A Crucial Role of INF-gamma in Experimental Autoimmune Prostatitis

Abstract

Purpose: An autoimmune etiology is proposed in some patients with chronic nonbacterial prostatitis since they show interferon-γ secreting lymphocytes specific to prostate antigens in the periphery and increased interferon-γ in seminal plasma. We investigated the involvement of interferon-γ in an animal model of autoimmune prostatitis. Materials and Methods: Experimental autoimmune prostatitis was studied in the no-obese diabetic and C57Bl/6 (Harlan, Zeist, The Netherlands) susceptible mouse strains, and in the IRF-1 KO and STAT-1 KO mouse strains deficient in transcription factors involved in interferon-γ signaling. Results: Experimental autoimmune prostatitis was characterized by prostate specific interferon-γ secreting cells in the periphery and by T-helper 1 related cytokines in the target organ. Increased interferon-γ and interleukin-12 were observed in the prostate of autoimmune animals while interleukin-10 and interleukin-4 were decreased and unaltered, respectively. The absence of transcription factors involved in the interferon-γ signaling cascade, IRF-1 and STAT-1, made mice resistant to experimental autoimmune prostatitis. IRF-1 KO and STAT-1 KO mice immunized with prostate antigens did not show infiltration or alterations in the prostate. They did not have the typical prostate specific autoimmune response and showed decreased interferon-γ, interleukin-12 and interleukin-10, and augmented interleukin-4 in the prostate. Conclusions: Our results argue for a crucial role of interferon-γ as a key factor in the pathogenesis of the disease. Intense research is promptly required to identify the pathogenic mechanisms underlying chronic prostatitis/chronic pelvic pain syndrome to find a more rational therapy.