Proinflammatory effects of exogenously administered IL-10 in experimental autoimmune orchitis

Kaneko, Tadayoshi; Itoh, Masahiro; Nakamura, Yoichi; Iimura, Akira; Hayashi, Shogo; Takahashi, Kodo; Stivala, Franca; Bendtzen, Klaus; Nicoletti, Ferdinando

doi:10.1016/s1043-4666(03)00103-0

Cited by 13 publications

(7 citation statements)

References 15 publications

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“…In EAO, adeno-associated virus-mediated human IL-10 gene transfer suppressed the development of the disease ( Watanabe et al 2005). However, it exerts the opposite effect in some autoimmune diseases including EAO (Rosenbaum & Angell 1995, Hill & Sarvertnick 2002, Kaneko et al 2003, Tokunaga et al 2008. Although pathophysiological effects of these two cytokines on the epididymal tissues remain unclear, the Vx-induced elevation of the epididymal cytokines may attract inflammatory cells to the epididymis rather than the testis.…”

Section: Effects Of Vasectomy On Testicular Autoimmunitymentioning

confidence: 99%

Caput epididymitis but not orchitis was induced by vasectomy in a murine model of experimental autoimmune orchitis

Terayama²,

Naito³

et al. 2008

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Immunization of mice with viable syngeneic testicular germ cells (TGC) alone can induce autoimmune responses against autoantigens of both round and elongating spermatids, resulting in the development of experimental autoimmune orchitis (EAO). Histological lesions in this EAO model without an adjuvant are characterized by lymphocytic infiltration into the testes, spermatogenic disturbance, and a complete lack of epididymitis. In this study, we investigated the effects of vasectomy (Vx) on TGC-induced EAO expecting that Vx augments the severity of testicular inflammation in A/J mice. The results showed that mice receiving Vx alone exhibited no significant inflammatory cell response in either the testes or epididymides, and mice receiving shamVxCTGC immunization had EAO with no epididymitis. In sharp contrast, no EAO was found in the testes of any mice receiving VxCTGC immunization. Instead, caput epididymitis involving CD4CT cells, CD8CT cells, B cells, and macrophages were induced in them with striking elevation of the tissue levels of both IL6 and IL10 mRNA. Furthermore, serum autoantibodies induced by shamVxCTGC immunization were reactive with both round (immature) and elongating (mature) spermatids; however, those induced by VxCTGC immunization were specific to acrosomes of mature spermatids and spermatozoa. These unexpected results indicate that Vx may induce the mode by which autoreactive lymphocytes gain access to TGC autoantigens in the epididymides, leading to autoimmune responses against the autoantigens of mature rather than immature spermatids. Reproduction (2008) 135 859-866

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Section: Effects Of Vasectomy On Testicular Autoimmunitymentioning

confidence: 99%

Caput epididymitis but not orchitis was induced by vasectomy in a murine model of experimental autoimmune orchitis

Terayama²,

Naito³

et al. 2008

Reproduction

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“…Further support for a high Th1 ⁄ Th2 ratio-dependent pathogenesis of EAO comes from our recent observation that the disease can be prevented by the injection of recombinant IL-6, a Th2-secreting cytokine (Li et al, 2002). On the other hand, it was found that the injection of recombin-ant IL-10, another Th2 cytokine, increased the EAO severity, suggesting that IL-10 has played an autoimmne-promoting cytokine rather than a regulatory cytokine (Kaneko et al, 2003). In contrast, in EAO induced by testicular trauma, Watanabe et al (2005) recently demonstrated that intramuscular injections of adeno-associated virus-mediated human IL-10 significantly suppressed testicular trauma-induced EAO.…”

Section: Discussionmentioning

confidence: 97%

“…, 2002). On the other hand, it was found that the injection of recombinant IL‐10, another Th2 cytokine, increased the EAO severity, suggesting that IL‐10 has played an autoimmne‐promoting cytokine rather than a regulatory cytokine (Kaneko et al. , 2003).…”

Section: Discussionmentioning

confidence: 99%

Splenic cytokines in mice immunized with testicular germ cells

et al. 2008

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We previously established that two subcutaneous injections of viable syngeneic testicular germ cells (TGC) alone can induce CD4+ T cell-dependent experimental autoimmune orchitis (EAO) in mice. This model is histologically characterized by lymphocytic infiltration into the testes and the following aspermatogenesis. In the present study, we investigated the dynamics of splenic cytokines in EAO, using specific enzyme-linked immunosorbent assay. We found that splenic production of both type 1 helper T cell (Th1) and type 2 helper T cell (Th2)-related cytokines increased after the second but not the first immunization with TGC, indicating that secondary immune responses are critical to the EAO induction. However, the production of Th1-related cytokines became predominant at the clinical stage of EAO. Additionally, serum FSH and inhibin-B increased and decreased, respectively, during EAO. On the other hand, LH did not significantly change and testosterone temporally increased during the same period. These results indicate that both Th1- and Th2-related cytokines are involved at the pre-clinical phase of EAO, but that Th1- rather than Th2-related cytokines are responsible for the clinical phase when spermatogenesis is disrupted but the Leydig cell function is well preserved.

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“…IL-10 is a known immunesuppressive cytokine with a complementary relation to IFN-γ [28]. Also, IL-10 has pro-inflammatory functions, upregulating testicular immunoinflammatory processes by its systemic administration [29]. Therefore, it is possible that changes in cytokines in the testis after exposure to DEHP may induce spermatogenic disturbance.…”

Section: Discussionmentioning

confidence: 99%

Effects on the Local Immunity in the Testis by Exposure to Di-(2-ethylhexyl) Phthalate (DEHP) in Mice

Kitaoka

Hirai

Terayama

et al. 2013

Journal of Reproduction and Development

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Exposure to di-(2-ethylhexyl) phthalate (DEHP) has been reported to induce spermatogenic disturbance through oxidant stress and affect the immune system as an adjuvant. However, the effect of DEHP on the testicular immune microenvironment has not yet been investigated. In the present study, we examined the testicular immune microenvironment after exposure to doses of DEHP, previously identified as no-observed-adverse-effect levels. Adult male mice were administered food containing 0%, 0.01% or 0.1% DEHP and then testes were analyzed. The results showed that a slight but significant spermatogenic disturbance appeared in the 0.1% DEHP group but not in the 0.01% DEHP group at 8 weeks. It was also demonstrated that lymphocytes and F4/80- and MHC class II- positive cells were significantly increased with the elevation of IL-10 and IFN-γ mRNA expressions in the testes of not only the 0.1% DEHP group but also the 0.01% DEHP group at 8 weeks. Histochemical analyses involving horseradish peroxidase (HRP) as a tracer showed that a little blood-borne HRP had infiltrated into the lumen of a few seminiferous tubules beyond the blood-testis-barrier in both the 0.1% and 0.01% DEHP groups at 8 weeks. This indicates that a dose of DEHP that has little effects on spermatogenesis can change the testicular immune microenvironment with functional damage of the blood-testis barrier.

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Proinflammatory effects of exogenously administered IL-10 in experimental autoimmune orchitis

Cited by 13 publications

References 15 publications

Caput epididymitis but not orchitis was induced by vasectomy in a murine model of experimental autoimmune orchitis

Caput epididymitis but not orchitis was induced by vasectomy in a murine model of experimental autoimmune orchitis

Splenic cytokines in mice immunized with testicular germ cells

Effects on the Local Immunity in the Testis by Exposure to Di-(2-ethylhexyl) Phthalate (DEHP) in Mice

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