Prostate-specific antigen induces proliferation of peripheral blood lymphocytes and cytokine secretion in benign prostate hypertrophy patients.
OBJECTIVE
The etiology of benign prostatic hypertrophy (BPH) is still obscure. Data supporting an interaction connecting prostate hyperplasia and immune dysregulation is accumulating lately. The aim of the study was to assess the cellular immune responses to PSA by measuring the in vitro potential of PSA to induce proliferation and cytokine secretion in peripheral blood lymphocytes (PBLs) of BPH patients.


METHODS
PBLs were extracted from fresh blood of 36 BPH patients and 11 age-matched controls. The PBLs were incubated with PSA. Proliferation of the cultured PBLs was determined by thymidine incorporation. Secretion of cytokines to the culture medium was measured either by biological assay (IL-2) or by ELISA (IL-4, IL-10, IFNgamma, TNFalpha).


RESULTS
Twelve of the 36 BPH patients responded to PSA, whereas none of the 11 controls responded (p = 0.04). The proliferative response of PBLs from BPH patients was significantly higher as compared to PBLs of controls (p = 0.03). The mean total prostate volume and the transition zone volume were 51% and 54% bigger, respectively, among the responders to PSA as compared to the nonresponders (p < 0.05), whereas the mean serum PSA level did not differ significantly. PBLs of BPH patients secreted significantly higher levels of TNFalpha, both spontaneously and in response to PSA, as compared to controls (p = 0.003).


CONCLUSIONS
These findings show that PSA is able to induce proliferation of PBLs in vitro in BPH patients. Moreover, the higher spontaneous and PSA-induced secretion of TNFalpha in BPH patients may reflect a role for this proinflammatory cytokine in vivo. Based on these observations, we suggest that autoimmune dysregulation might have a role in BPH.
Zisman
A
A
Urology Department, Assaf Harofeh' Medical Center, Zerifin, Israel.
Lindner
A
A
Zisman
E
E
Lindner
U
U
Mozes
E
E
D000368:Aged; D000704:Analysis of Variance; D001707:Biopsy, Needle; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis*; D007378:Interleukins / Q000032:analysis*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000378:metabolism* / Q000494:pharmacology; D011470:Prostatic Hyperplasia / Q000276:immunology* / Q000473:pathology; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D016207:Cytokines; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D017430:Prostate-Specific Antigen