Urodynamic and ecographic studies have shown a high prevalence of urodynamic abnormalities. Are these under-diagnosed in male urologic patients? The problem with any of the above conditions is: what came first? In some cases physiological changes may be the obvious precursor, in other case they may be caused by the subsequent chronic inflammation. Urography and trans-rectal ultrasound should be performed to rule out these problems.
CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb, miktionsfysiologi, miktion, urodynamic findings, ultrasonography.
Wednesday, December 23, 2009
Tuesday, December 22, 2009
Varicocele and hemorrhoids
A higher prevalence of varicocele (=varicose veins in the scrotum) has been found in “chronic prostatitis syndrome” (sorry the category is from the study, but I guess NIH-III can be assumed) patients. About 15% were affected compared to 5% of the asymptomatic controls.(1-2)
CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb, miktionsfysiologi, miktion, urodynamic findings, varicocele, hemorrhoids.
_______________
(1) Pavone C, Caldarera E, Liberti P et al. Correlation between chronic prostatitis syndrome and pelvic venous disease: a survey of 2554 urologic outpatients. Eur Urol 37(4):400-403 2000
(2) Lotti F, Corona G, Mancini M, Biagini C, Colpi GM, Innocenti SD, Filimberti E, Gacci M, Krausz C, Sforza A, Forti G, Mannucci E, Maggi M. The Association between Varicocele, Premature Ejaculation and Prostatitis Symptoms: Possible Mechanisms. J Sex Med. 2009 Aug 11. [Epub ahead of print]
CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb, miktionsfysiologi, miktion, urodynamic findings, varicocele, hemorrhoids.
_______________
(1) Pavone C, Caldarera E, Liberti P et al. Correlation between chronic prostatitis syndrome and pelvic venous disease: a survey of 2554 urologic outpatients. Eur Urol 37(4):400-403 2000
(2) Lotti F, Corona G, Mancini M, Biagini C, Colpi GM, Innocenti SD, Filimberti E, Gacci M, Krausz C, Sforza A, Forti G, Mannucci E, Maggi M. The Association between Varicocele, Premature Ejaculation and Prostatitis Symptoms: Possible Mechanisms. J Sex Med. 2009 Aug 11. [Epub ahead of print]
Monday, December 21, 2009
Concretions / calculi / calcifications
These are hardened grains that can form in the bladder, prostate or ductus deferens and ejaculatorius. The composition of prostatic calculi indicates that they too are caused by reflux.(1) Small concretions occur in healthy men, but men with many or larger ones have shown improvement upon elimination of those.(2-3)
CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb, miktionsfysiologi, miktion, urodynamic findings,calculi, prostate, ductus deferens.
_________________
(1) http://www.prostatitis.org/stones.html
(2) Geramoutsos I, Gyftopoulos K, Perimenis P, Thanou V, Liagka D, Siamblis D et al. Clinical correlation of prostatic lithiasis with Chronic Pelvic Pain Syndromes in Young Adults. Eur Urol 45(3):333-338, 2004.
(3) Shoskes DA, Lee CT, Murphy D, Kefer J, Wood HM. Incidence and significance of prostatic stones in men with chronic prostatitis/chronic pelvic pain syndrome. Urology 70(2):235-238, 2007.
CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb, miktionsfysiologi, miktion, urodynamic findings,calculi, prostate, ductus deferens.
_________________
(1) http://www.prostatitis.org/stones.html
(2) Geramoutsos I, Gyftopoulos K, Perimenis P, Thanou V, Liagka D, Siamblis D et al. Clinical correlation of prostatic lithiasis with Chronic Pelvic Pain Syndromes in Young Adults. Eur Urol 45(3):333-338, 2004.
(3) Shoskes DA, Lee CT, Murphy D, Kefer J, Wood HM. Incidence and significance of prostatic stones in men with chronic prostatitis/chronic pelvic pain syndrome. Urology 70(2):235-238, 2007.
Sunday, December 20, 2009
Urodynamic problems and intraprostatic pressure
An often overlooked factor seems to be screening for physiological and mechanical and fluid dynamical causes related to bladder, prostate and seminal vesicles. Studies have found physical abnormalities, and a transrectal ultrasonography study found physical (urological) abnormalities or other conditions in as many as 70% of the patients ! (1)
The most common cause of pathology is reflux(2), or urine flow up into the canalicoli (i.e. prostate) is caused by urethral strictures (due to trigonitis or urethral stenosis, both uncommon in men, or muscular hypertonus or physical abnormalities(3)) or sclerosis/dysectasia of the bladder neck (cervicis vesicae) affecting normal defluition (“deflux”) of urine (micturition). Non-infectious epidydimitis may also occur for the same reasons. Reflux is thought to cause inflammation by the presence of purine and pyrimidine (uric acid) in the urine. (Aside: high values of uric acid in blood causes gout.) Another possible cause of inflammation could be turbulent flow of the urine damaging urethral tissues.(4)
A recent ultrasound study of the bladder neck area found differences of: prostate volume, hypoechoic periurethral zone volume, posterior prostate lip thickness, bladder neck thickness and bladder muscle (detrusor) thickness between CPPS patients and controls. No differences in calcifications were found.(5)
A study indicated that NIH-IIIa patients have significantly higher intraprostatic pressure than IIIb or BPH patients(6), This may be caused by strictures, as mentioned above, muscular tension or concretions, or by tissue damage caused by blood pressure and other problems affecting interstitial tissue pressure.(7) This latter would also be consistent with the presence of inflammation markers.
Fall et al. concluded that: “Urodynamic studies [of prostatitis patients] demonstrate decreased urinary flow rates, incomplete relaxation of the bladder neck and prostatic urethra, as well as abnormally high urethral closure pressure at rest. The relaxation of the external urethral sphincter during urination is normal”.
CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb, miktionsfysiologi, miktion, urodynamic findings, intraprostatic pressure, ultrasonography, reflux. stenosis, trigonitis, varicocele, detrusor, urethral sphincter.
____________________
(1) Nicolai M, De Thomasis R, Di Federico G, Palmerio A, Iantorno R, Tenaglia R. [Role of transrectal echography in the evaluation of obstructive seminal vesicle pathology in prostatitis syndrome] Arch Ital Urol Androl. 68 (5 Suppl):101-4, 1996.
(2) Mehik A, Leskinen MJ, Hellström P Mechanisms of pain in CPPS: influence of prostatic inflammation. World J urol 21:90-94, 2003
(3) Hochreiter WW Zbrun S CPPS and voiding dysfunction. Curr Urol Rep 5(4):300-304, 2004
(4) Martinez-Borges AR Turbulent urinary flow in the urethra could be a causal factor for benign prostatic hyperplasia. Medical hypothesis 67(4):871-875 2006
(5) Dellabella M, Milanese G, Muzzonigro G. Ultrasound evaluation of bladder neck complex alterations in CP/CPPS. 2005 EAU meeting, Istanbul. (Also published in J Urol 176:112-118, 2006. Correlation between…)
(6) Mehik A, Hellstrom P, Nickel JC et al The CP/CPPS can be characterized by prostatic tissue pressure measurements. J Urol 167(1):137-140, 2002
(7) Mehik A, Leskinen MJ, Hellström P Mechanisms of pain in CPPS: influence of prostatic inflammation. World J urol 21:90-94, 2003
The most common cause of pathology is reflux(2), or urine flow up into the canalicoli (i.e. prostate) is caused by urethral strictures (due to trigonitis or urethral stenosis, both uncommon in men, or muscular hypertonus or physical abnormalities(3)) or sclerosis/dysectasia of the bladder neck (cervicis vesicae) affecting normal defluition (“deflux”) of urine (micturition). Non-infectious epidydimitis may also occur for the same reasons. Reflux is thought to cause inflammation by the presence of purine and pyrimidine (uric acid) in the urine. (Aside: high values of uric acid in blood causes gout.) Another possible cause of inflammation could be turbulent flow of the urine damaging urethral tissues.(4)
A recent ultrasound study of the bladder neck area found differences of: prostate volume, hypoechoic periurethral zone volume, posterior prostate lip thickness, bladder neck thickness and bladder muscle (detrusor) thickness between CPPS patients and controls. No differences in calcifications were found.(5)
A study indicated that NIH-IIIa patients have significantly higher intraprostatic pressure than IIIb or BPH patients(6), This may be caused by strictures, as mentioned above, muscular tension or concretions, or by tissue damage caused by blood pressure and other problems affecting interstitial tissue pressure.(7) This latter would also be consistent with the presence of inflammation markers.
Fall et al. concluded that: “Urodynamic studies [of prostatitis patients] demonstrate decreased urinary flow rates, incomplete relaxation of the bladder neck and prostatic urethra, as well as abnormally high urethral closure pressure at rest. The relaxation of the external urethral sphincter during urination is normal”.
CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb, miktionsfysiologi, miktion, urodynamic findings, intraprostatic pressure, ultrasonography, reflux. stenosis, trigonitis, varicocele, detrusor, urethral sphincter.
____________________
(1) Nicolai M, De Thomasis R, Di Federico G, Palmerio A, Iantorno R, Tenaglia R. [Role of transrectal echography in the evaluation of obstructive seminal vesicle pathology in prostatitis syndrome] Arch Ital Urol Androl. 68 (5 Suppl):101-4, 1996.
(2) Mehik A, Leskinen MJ, Hellström P Mechanisms of pain in CPPS: influence of prostatic inflammation. World J urol 21:90-94, 2003
(3) Hochreiter WW Zbrun S CPPS and voiding dysfunction. Curr Urol Rep 5(4):300-304, 2004
(4) Martinez-Borges AR Turbulent urinary flow in the urethra could be a causal factor for benign prostatic hyperplasia. Medical hypothesis 67(4):871-875 2006
(5) Dellabella M, Milanese G, Muzzonigro G. Ultrasound evaluation of bladder neck complex alterations in CP/CPPS. 2005 EAU meeting, Istanbul. (Also published in J Urol 176:112-118, 2006. Correlation between…)
(6) Mehik A, Hellstrom P, Nickel JC et al The CP/CPPS can be characterized by prostatic tissue pressure measurements. J Urol 167(1):137-140, 2002
(7) Mehik A, Leskinen MJ, Hellström P Mechanisms of pain in CPPS: influence of prostatic inflammation. World J urol 21:90-94, 2003
Nocturia and quality of life
A couple of months ago I discussed how nocturia affects neurological health. Below follows a diagram presented at the EAU 2009 in Stockholm (based on Tikkinen et al poster presented at ICS 2008, abstract 434). It illustrates well how even one nocturnal void affects quality of life (QoL).
CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb, miktionsfysiologi, miktion.
CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb, miktionsfysiologi, miktion.
Vitamin D and immune seasonality
Many diseases show an increased incidence with less sun exposure (i.e. living in the north) which may be correlated insufficient levels vitamin D. Does vitamin D affect immune regulation? Yes, an increasing amount of evidence shows that vitamin D and individual vitamin D receptor polymorphism (“gene variants”) are very important for immune regulation. The VDR is present in almost every cell in the body. Much of the basic research has been done with so called VDR null (3) mice and it indicates that VDR differences in vitamin D deficiency cause different risk for respiratory diseases, stomach ulcers, auto-immunity, cancers (breast, skin, colon, prostate, pancreas etc), hypertension, IBS, diabetes, increased thrombogenicity (“clot forming”), thyroid disturbances, rheumatic disease, MS (4) (which “is essentially unknown at the equator”), osteoporosis, diffuse muscular pain, ostearthrosis, connective tissue disorders, caries, skin disorders (including acne), rickets, SLE, myopathy (“weak muscles”), schizophrenia and on and on and on.
Main ways of action of vitamin D (or rather its metabolites) are immuno-regulatory. It regulates immunity by suppressing the proliferation of immunoglobulin, inhibit differentiation of dendritic cells (“the most potent of antigen presenting cells”), slowing B cell differentiation and inhibit Th1 cell proliferation (innate, cellular response) thus decreasing e.g. IFN-gamma and IL-2 productiion. It may also increase Treg and IL-4, 5 and 10 production thus in sum inducing a more Th2 (adaptive, humoral) biased response and attenuating any excessive Th1 inflammatory response.. It does also regulate and inhibit Th17 response. Innate immunity is also enhanced by expression of antimicrobial peptides (AMPs, e.g. cathelicidin and defensins). Innate (cellular) immunity is important for epithelial integrity of e.g. lungs, gengiva, bladder, skin (epidermis) and intestine. VDR-driven immune response is strongly impaired in vitamin D deficiency. Other effects are anti-neoplastic (regulation of cell growth and differentiation) and inhibition of angiogenesis (growth of new blood vessels, especially into tumors). Influenza and auto-immune disease are typically worsening (exacerbating / flaring) in winter (3) and spring, and improving in summer and fall.(4-12)
125 micrograms vitamin D per day reach steady state at about 150 nmol/l 25(OH)D after 3 months and 250 micrograms at about 200 nmol/l after 3 months (starting point was 70 nmol).(13) Intoxication has been observed at levels above 375 nmol/l (50000 IU/day). Skin production of vitamin D is self-limiting so intoxication is not possible by tanning. Hyperthyroidism increases 25(OH)D metabolism rates. (Holick)
Useful amounts of vitamin D are only present in certain wild fat fish. E.g. fresh *wild* salmon that contains 600-1000 IU per 100 grams. Darkskinned African skin equals approximately a sun protection factor 15 sun screen (Holick).
CPPS, prostatit, kroniskt bäckenbottensmärtsyndrom, nokturi, trängningar, immunity, seasonality, D-vitamin, auto-immune disease.
_________________
(1) Caveat: murine immune system differs from human in certain important aspects.
(2) In a trial reported by J Burton, at the 2009 meeting of American Academy of Neurology, vitamin D supplementation for, on average, 14000 IU/day induced remission and about a halved relapse rate.
(3) Immune response is upregulated during winter to counter environmental adversities. In the wild the net effect is a relative immune suppression (due to limited energy availability / high energy expense), but in laboratory conditions this may not be the case.
(4) Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, Lieben L, Mathieu C, Demay M. Vitamon D and human health: lesosn from vitamin D receptor null mice. Endocr Rev 29(6):726-776, 2008.
(5) Cantorna MT. Vitamin D and its role in immunology: multiple sclerosis and inflammatory bowel disease. Prog Biophys Mol Biol. 92(1):60-64, 2006.
(6) Lips P. Vitamin D physiology. Prog Biophys Mol Biol. 92(1):4-8, 2006.
(7) Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc 81:353-373, 2006.
(8) Holick MF. Vitamin D deficiency. NEJM 357(3):266-281, 2007.
(9) Mouyis M, Ostor AJK, Crisp AJ, Ginawi A, Halsall DJ, Shenker N, Poole KES. Hypovitaminosis D among rheumatology outpatients in clinical practice. Rheumatology 47:1348-1351, 2008.
(10) Nelson RJ. Seasonal immune function and sickness response. Trends Immunol 25(4):187-192, 2004.
(11) Bikle D. Nonclassic actions of vitamin D. J Clin Endocrinol Metab 94(1):26-34, 2009.
(12) White JH. Vitamin D signaling, infectious diseases and regulation of innate immunity. Inf Immun 76(9):3837-3843, 2008.
(13) Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr 77:204-210, 2003.
Main ways of action of vitamin D (or rather its metabolites) are immuno-regulatory. It regulates immunity by suppressing the proliferation of immunoglobulin, inhibit differentiation of dendritic cells (“the most potent of antigen presenting cells”), slowing B cell differentiation and inhibit Th1 cell proliferation (innate, cellular response) thus decreasing e.g. IFN-gamma and IL-2 productiion. It may also increase Treg and IL-4, 5 and 10 production thus in sum inducing a more Th2 (adaptive, humoral) biased response and attenuating any excessive Th1 inflammatory response.. It does also regulate and inhibit Th17 response. Innate immunity is also enhanced by expression of antimicrobial peptides (AMPs, e.g. cathelicidin and defensins). Innate (cellular) immunity is important for epithelial integrity of e.g. lungs, gengiva, bladder, skin (epidermis) and intestine. VDR-driven immune response is strongly impaired in vitamin D deficiency. Other effects are anti-neoplastic (regulation of cell growth and differentiation) and inhibition of angiogenesis (growth of new blood vessels, especially into tumors). Influenza and auto-immune disease are typically worsening (exacerbating / flaring) in winter (3) and spring, and improving in summer and fall.(4-12)
125 micrograms vitamin D per day reach steady state at about 150 nmol/l 25(OH)D after 3 months and 250 micrograms at about 200 nmol/l after 3 months (starting point was 70 nmol).(13) Intoxication has been observed at levels above 375 nmol/l (50000 IU/day). Skin production of vitamin D is self-limiting so intoxication is not possible by tanning. Hyperthyroidism increases 25(OH)D metabolism rates. (Holick)
Useful amounts of vitamin D are only present in certain wild fat fish. E.g. fresh *wild* salmon that contains 600-1000 IU per 100 grams. Darkskinned African skin equals approximately a sun protection factor 15 sun screen (Holick).
CPPS, prostatit, kroniskt bäckenbottensmärtsyndrom, nokturi, trängningar, immunity, seasonality, D-vitamin, auto-immune disease.
_________________
(1) Caveat: murine immune system differs from human in certain important aspects.
(2) In a trial reported by J Burton, at the 2009 meeting of American Academy of Neurology, vitamin D supplementation for, on average, 14000 IU/day induced remission and about a halved relapse rate.
(3) Immune response is upregulated during winter to counter environmental adversities. In the wild the net effect is a relative immune suppression (due to limited energy availability / high energy expense), but in laboratory conditions this may not be the case.
(4) Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, Lieben L, Mathieu C, Demay M. Vitamon D and human health: lesosn from vitamin D receptor null mice. Endocr Rev 29(6):726-776, 2008.
(5) Cantorna MT. Vitamin D and its role in immunology: multiple sclerosis and inflammatory bowel disease. Prog Biophys Mol Biol. 92(1):60-64, 2006.
(6) Lips P. Vitamin D physiology. Prog Biophys Mol Biol. 92(1):4-8, 2006.
(7) Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc 81:353-373, 2006.
(8) Holick MF. Vitamin D deficiency. NEJM 357(3):266-281, 2007.
(9) Mouyis M, Ostor AJK, Crisp AJ, Ginawi A, Halsall DJ, Shenker N, Poole KES. Hypovitaminosis D among rheumatology outpatients in clinical practice. Rheumatology 47:1348-1351, 2008.
(10) Nelson RJ. Seasonal immune function and sickness response. Trends Immunol 25(4):187-192, 2004.
(11) Bikle D. Nonclassic actions of vitamin D. J Clin Endocrinol Metab 94(1):26-34, 2009.
(12) White JH. Vitamin D signaling, infectious diseases and regulation of innate immunity. Inf Immun 76(9):3837-3843, 2008.
(13) Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr 77:204-210, 2003.
Saturday, December 19, 2009
The immune system (enteric, gender, seasonality)
The following blog posts will discuss basic immune function and the possible connections with CPPS.
The immune system is divided in two arms: innate and adaptive. Both of which contain cellular (macrophages, natural killer cells etc) and humoral (antibodies) immune components. Cellular immunity protects mainly against intracellular bacteria, protozoans, fungi and many viruses), while humoral immunity protects against multicellular parasites, extracellular bacteria, certain viruses, ceratin toxins and allergens. A popular concept of immunity is the Th1/Th2/Th17-hypothesis.(1-3) In additon to these two arms, an oft forgotten an very important part of the immune system is the enteric immune system.
Not only does the gut have a massive nervous system (see below), it is also the biggest immune system in the body. The gut-associated lymphoid tissue comprises about 70 percent of the mucosal barrier (most of the rest protects the lungs). And that is not suprising as the gut has to withstand an endless stream of pathogens and occasional toxins. Not only invaders from outside the body but also the about over 100 trillion organisms that live in the gut. The maternal intestinal microbiota (both organisms and a large number of “intestinally derived bacterial components”, N.B. not antibodies, but genetic material) is passed to the newborn trough the breast milk.(4) Ingested probiotics may modulate intestinal pain and the immune system by normalizing cytokine ratios.(5)
The brain and the viscera communicate with each other to coordinate behavior and emotional responses (due to evolutionary reasons like territorial marking, not stop to pee while hunted, panic, anxiety, and so on).and visceral activity. Pathological changes (e.g. bacterial infection, tissue damage, distension of the colon and others) in the viscera affect the forebrain.
Immune activity shows a circadian rhythm with cellular/Th1 prevalence during sleep (maximum activity coincides with nocturnal cortisol maximum) and humoral/Th2 prevalence during daytime. Diseases more common / worse during daytime are e.g. stroke, arrhythmias, seizures, sepsis and asthma.
A seasonal pattern of increased immune activity during winter with humoral bias, to counter wintertime stress induced immune suppression, and cellular bias during summer is also postulated.(6,7) Children (and especially foetuses) are more humoral/Th2 biased than adults (8) (and sex differences are minimal before puberty). Adult men generally have a more Th1-biased response, due to high androgen levels, that gets more Th2-biased with age as testosterone levels decrease. Female response is generally more Th2-biased due to the high levels of estrogens that are both pro-inflammatory (a pro-fibrotic response) and “immunosupportive”. Thus the same infectious (or adjuvant) insult may cause a stronger anti-inflammatory response in men.(9)
Estrogens correlate with increased incidence of depression, axiety and auto-immune disorders (women are 2-9 times more likely to suffer from pain disorders, RA and SLE). Female immune response varies with the different phases of the menstrual cycle, pregnancy and contraceptive usage.(10)
Much confusion casued by animals studies arises from the fact that acute and chronic phase response are not distinguished. These differences between acute and chronic phases and phases of the menstrual cycle are seldom considered in general research even if sex differences have been accounted for (which in itself is not done as much as it should).
Nocturia induced sleep disruption and androgen alterations may both lead to immune changes worsening CPPS and explain the sickness behaviour seen in CPPS sufferers. Also the fact that CPPS generally remits during summer (when sun-stimulated vitamin D production shift the immune response towards an anti-inflammatory response), may indicate that CPPS is an immune related disorder. Possibly a disorder of Th1-driven (cellular) inflammatory immunity.
CPPS, prostatit, kroniskt bäckenbottensmärtsyndrom, nokturi, trängningar, enteric, gender immune dimorphism, immunity, Th1/Th2, androgens, estrogens, nocturia, seasonality.
______________________
(1) Steinman L. A rush to judgment on Th17. J Exp Med 205(7): 1517–1522, 2008.
(2) Kidd P. Th1/Th2 balance: The hypothesis, its limitations, and implications for health and disease. Altern Med Rev 8(3):223-246, 2003
(3) Steinman L. A brief history of TH17, the first major revision in the TH1/TH2 hypothesis of T cell–mediated tissue damage. Nature medicine 13(2):139-145, 2007
(4) Perez PF, Dore J, Leclerc M, Levenez F, Benyacoub J, Serrant P, Segira-Roggero I, Schiffrin EJ, Donnet-Hughes A. Bacterial imprinting on the neonatal immune system: lessons from maternal cells? Pediatrics 119(3):E724-732, 2007.
(5) Marchesi J, Shanahan F. The normal intestinal microbiota. Curr Opin Infect Dis 20:508-513, 2007.
(6) Nelson RJ, GE Demas GE, Klein SL, Kriegsfeld LJ. Seasonal Patterns of Stress, Immune Function, and Disease. Cambridge University Press, 2002.
(7) Nelson RJ. Seasonal immune function and sickness responses Trends in Immunology 25(4):187-192, 2004.
(8) Petrovsky N. Towards a unified model of neuroendocrine–immune interaction. Immunol Cell Biol 79:350–357, 2001
(9) Fairweather D, Frisancho-Kiss S, Rose NR. Sex differences in autoimmune disease from a pathological perspective. Am J Pathol 173:600-609, 2008.
(10) Darnall BD, Suarez EC. Sex and gender in psychoneurimmunology research: past, present and future. Brain Behav Immun 23:595-604, 2009.
The immune system is divided in two arms: innate and adaptive. Both of which contain cellular (macrophages, natural killer cells etc) and humoral (antibodies) immune components. Cellular immunity protects mainly against intracellular bacteria, protozoans, fungi and many viruses), while humoral immunity protects against multicellular parasites, extracellular bacteria, certain viruses, ceratin toxins and allergens. A popular concept of immunity is the Th1/Th2/Th17-hypothesis.(1-3) In additon to these two arms, an oft forgotten an very important part of the immune system is the enteric immune system.
Not only does the gut have a massive nervous system (see below), it is also the biggest immune system in the body. The gut-associated lymphoid tissue comprises about 70 percent of the mucosal barrier (most of the rest protects the lungs). And that is not suprising as the gut has to withstand an endless stream of pathogens and occasional toxins. Not only invaders from outside the body but also the about over 100 trillion organisms that live in the gut. The maternal intestinal microbiota (both organisms and a large number of “intestinally derived bacterial components”, N.B. not antibodies, but genetic material) is passed to the newborn trough the breast milk.(4) Ingested probiotics may modulate intestinal pain and the immune system by normalizing cytokine ratios.(5)
The brain and the viscera communicate with each other to coordinate behavior and emotional responses (due to evolutionary reasons like territorial marking, not stop to pee while hunted, panic, anxiety, and so on).and visceral activity. Pathological changes (e.g. bacterial infection, tissue damage, distension of the colon and others) in the viscera affect the forebrain.
Immune activity shows a circadian rhythm with cellular/Th1 prevalence during sleep (maximum activity coincides with nocturnal cortisol maximum) and humoral/Th2 prevalence during daytime. Diseases more common / worse during daytime are e.g. stroke, arrhythmias, seizures, sepsis and asthma.
A seasonal pattern of increased immune activity during winter with humoral bias, to counter wintertime stress induced immune suppression, and cellular bias during summer is also postulated.(6,7) Children (and especially foetuses) are more humoral/Th2 biased than adults (8) (and sex differences are minimal before puberty). Adult men generally have a more Th1-biased response, due to high androgen levels, that gets more Th2-biased with age as testosterone levels decrease. Female response is generally more Th2-biased due to the high levels of estrogens that are both pro-inflammatory (a pro-fibrotic response) and “immunosupportive”. Thus the same infectious (or adjuvant) insult may cause a stronger anti-inflammatory response in men.(9)
Estrogens correlate with increased incidence of depression, axiety and auto-immune disorders (women are 2-9 times more likely to suffer from pain disorders, RA and SLE). Female immune response varies with the different phases of the menstrual cycle, pregnancy and contraceptive usage.(10)
Much confusion casued by animals studies arises from the fact that acute and chronic phase response are not distinguished. These differences between acute and chronic phases and phases of the menstrual cycle are seldom considered in general research even if sex differences have been accounted for (which in itself is not done as much as it should).
Nocturia induced sleep disruption and androgen alterations may both lead to immune changes worsening CPPS and explain the sickness behaviour seen in CPPS sufferers. Also the fact that CPPS generally remits during summer (when sun-stimulated vitamin D production shift the immune response towards an anti-inflammatory response), may indicate that CPPS is an immune related disorder. Possibly a disorder of Th1-driven (cellular) inflammatory immunity.
CPPS, prostatit, kroniskt bäckenbottensmärtsyndrom, nokturi, trängningar, enteric, gender immune dimorphism, immunity, Th1/Th2, androgens, estrogens, nocturia, seasonality.
______________________
(1) Steinman L. A rush to judgment on Th17. J Exp Med 205(7): 1517–1522, 2008.
(2) Kidd P. Th1/Th2 balance: The hypothesis, its limitations, and implications for health and disease. Altern Med Rev 8(3):223-246, 2003
(3) Steinman L. A brief history of TH17, the first major revision in the TH1/TH2 hypothesis of T cell–mediated tissue damage. Nature medicine 13(2):139-145, 2007
(4) Perez PF, Dore J, Leclerc M, Levenez F, Benyacoub J, Serrant P, Segira-Roggero I, Schiffrin EJ, Donnet-Hughes A. Bacterial imprinting on the neonatal immune system: lessons from maternal cells? Pediatrics 119(3):E724-732, 2007.
(5) Marchesi J, Shanahan F. The normal intestinal microbiota. Curr Opin Infect Dis 20:508-513, 2007.
(6) Nelson RJ, GE Demas GE, Klein SL, Kriegsfeld LJ. Seasonal Patterns of Stress, Immune Function, and Disease. Cambridge University Press, 2002.
(7) Nelson RJ. Seasonal immune function and sickness responses Trends in Immunology 25(4):187-192, 2004.
(8) Petrovsky N. Towards a unified model of neuroendocrine–immune interaction. Immunol Cell Biol 79:350–357, 2001
(9) Fairweather D, Frisancho-Kiss S, Rose NR. Sex differences in autoimmune disease from a pathological perspective. Am J Pathol 173:600-609, 2008.
(10) Darnall BD, Suarez EC. Sex and gender in psychoneurimmunology research: past, present and future. Brain Behav Immun 23:595-604, 2009.
Some final words on androgens
As androgens, and especially testosterone, are important for male health they are an interesting field of research. Unfortunately the research is scant on the relation between androgens and CPPS. But it is definitively a good idea to try to minimize androgen disruption by trying to get enough sleep. Especially due to the fact that nocturia disrupts sleep in CPPS. A possible solution could be very small doses of desmopressin, to see if sleep improves leading to improved wellbeing and vigour. It would also be interesting to research thyroid and gonadal-pituitary function.
CPPS, prostatit, kroniskt bäckenbottensmärtsyndrom, nokturi, trängningar, androgens, erection, estrogens, nocturia, testosterone.
CPPS, prostatit, kroniskt bäckenbottensmärtsyndrom, nokturi, trängningar, androgens, erection, estrogens, nocturia, testosterone.
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