Is immune function in CPPS abnormal?

In CPPS “the baseline epinephrine output (but not cortisol and sex steroid hormones) correlated inversely with proinflammatory and positively with anti-inflammatory cytokine production. Thus, low vs high epinephrine excretors had a 2- to 5-fold higher TNF-alpha and IL-12 production but 2-fold lower IL-10 production induced by LPS. ...This indicates that baseline epinephrine conditions cytokine responsiveness and through this mechanism intrinsic hypo- or hyperactive adrenal medullas in some individuals may shape opposite cytokine profiles.”(1)

Interestingly CPPS improves during summer. Is it because of vitamin D regulation of immune function? Vitamin D is a potent immune regulator. It does e.g. downregulate excessive cellular response by inhibiting IL-12 and upregulating IL-10.

This may indicate CPPS sufferers are low epinephrine excretors (and thus have low IL-10) and have a hypoactive adrenal medulla. Which in turn may sustain a hypoactive SNS and cellular (Th1/Th17 biased) immune response (and thus autoimmunity).

Do CPPS sufferers have a low IL-10 phenotype? Actually it may be so. Shoskes et al and small Chinese study indicates a higher prevalence of low-IL-10 polymorphisms.(2,3) These are also more common in IBS(4), Crohn’s and other diseases. Another small Chinese study indicates the possibility of immune hypoactivity. They found that TGF-beta1 levels are lower and Foxp3 gene expression is defective.(5) IL-8, measured in seminal plasma, has also been found to be higher in CPPS, especially in NIH-IIIa and -IV.(6) NIH-IIIb has slightly elevated inflammatory markers, while –IIIa and IV have distinctly higher levels than IIIb. (The information about inflammatory immune response in CPPS is somewhat confusing, which is probably due to the fact that seasonal variation in disease activity is not accounted for -- in almost all the papers I have read. Vitamin D levels, for one, would have been interesting to know due to its effect on immune activity.)

IL-10 does also regulate IDO(7) expression, which has been proposed to mediate sickness behaviour, in cells derived from the HPA axis, leading to increased tryptophan availability for serotonin and melatonin pathways, which also may explain why CPPS sufferers feel better during summer.(8,9)

Estrogens (specifically E2, 17B-estradiol) has been shown (at female pregnancy levesl) in murine models to cause inflammation of the prostate histologically similar to those found in CP/CPPS (“chronic abacterial prostatitis”). Unfortunately estrogen levels have not been well studied in CPPS patients, but increased conversion to E2 has been found in SLE and RA. E2 has also been found to cause liver inflammation(10), which leads to increased SHBG levels and decreased free testosterone levels. Decreased testosterone should thus lead to amelioration, but other weak androgens may be converted to estrogens and thus sustain an inflammatory process. Unfortunately SHBG levels are also not studied in CPPS.

Andra bloggar om immunity, adrenal, cytokines, Th1/Th2, estrogens, SHBG, IL-6, HPA axis, IDO, IL-10, IL-12, hypoactive adrenal medulla, low epinephrine excretors.
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(1) Elenkov IJ, Kvetnansky R, Hashiramoto A, Bakalov VK, Link AA, Zachman K, Crane M, Jezova D, Rovensky J, Dimitrov MA, Gold PW, Bonini S, Fleisher T, Chrousos GP, Wilder RL. Low- versus high-baseline epinephrine output shapes opposite innate cytokine profiles: presence of Lewis- and Fischer-like neurohormonal immune phenotypes in humans? J Immunol 181(3):1737-1745, 2008.
(2) Peng FH, Yang JR, Peng LK, Xie XB. [Association of gene polymorphisms of cytokine and cytokine receptor with type III prostatitis] Zhonghua Nan Ke Xue 14(12):1069-1071, 2008. English abstract.
(3) Shoskes DA, Albakri Q, Thomas K, Cook D. Cytokine polymorphisms in men with chronic prostatitis/chronic pelvic pain syndrome: association with diagnosis and treatment response. J Urol. 168(1):331-335, 2002.
(4) Collins SM. Dysregulation of Peripheral Cytokine Production in Irritable Bowel Syndrome. Am J Gastroenterol 100:2517-2518, 2005.
(5) Wang SG, Bai J, Xi QL, Hu DL, Liu JH, Ye ZQ. [The role of CD4+CD25+ regulatory T cells in the pathogenesis of chronic abacterial prostatitis/chronic pelvic pain syndrome] Zhonghua Yi Xue Za Zhi. 88(40):2838-2841, 2008. English abstract.
(6) Penna G, Mondaini N, Amuchastegui S, Degli Innocenti S, Carini M, Giubilei G, Fibbi B, Colli E, Maggi M, Adorini L. Seminal plasma cytokines and chemokines in prostate inflammation: interleukin 8 as a predictive biomarker in CP/CPPS and BPH. J Eur Uro 51:524-533, 2007.
(7) Indoleamine 2,3-dioxygenase "is an that initiates the oxidative degradation of ... l-tryptophan, along the kynurenine pathway. The local cellular depletion ... may enable the host to inhibit the growth of various infectious pathogens ... IDO also represents an important immune control enzyme ... capable of suppressing local T cell responses to promote immune tolerance under [during] infectious diseases, foetal rejection, organ transplantation, neuropathology, inflammatory and auto-immune disorders and cancer". King NJ, Thomas SR. Molecules in focus: indoleamine 2,3-dioxygenase. Int J Biochem Cell Biol. 39(12):2167-72 2007.
(8) Tu, H, Rady P, Juelich T, Smith E, Tyring S, Hughes T. Cytokine Regulation of Tryptophan Metabolism in the Hypothalamic-Pituitary-Adrenal (HPA) Axis: Implications for Protective and Toxic Consequences in Neuroendocrine Regulation. Cell Mol Neurobiol 25(3-4):673-680, 2005.
(9) McNally L, Bhagwagar Z, Hannestad J. Inflammation, glutamate and glia in depression: a literature review. CNS Spectr 13(6):501-510, 2008.
(10) Straub RH. The complex role of estrogens in inflammation. Endocrine reviews 28(5):521-574.