Role of IL-5 during primary and secondary immune response to acetylcholine receptor

Complement and cytokine based therapeutic strategies in myasthenia gravis

“…By contrast, deficiency of other Th2 cytokines IL-5 and IL-10 render mice significantly resistant to EAMG induction [43,51]. AChR antibody production and AChR-specific proliferative responses are intact in IL-5 and IL-10 KO mice and the exact mechanisms rendering these strains EAMG resistance are not well understood.…”

“…For instance, C1q mediates IgG2b isotype switching and IL-6 production, CD59 intervenes with C3, C4 and IL-2 production and C3 enhances IL-6, IL-10 and IFN-g synthesis [4,25,38]. Likewise, EAMG associated cytokines IL-5, IL-6 and IFN-g promote the production of several complement factors [43,44,77]. Therefore, successful treatment models for EAMG can be innovated by combined inhibition of the cytokine and the complement systems, which appear to work in close relationship (Fig.…”

Myasthenia gravis: past, present, and future

“…63, 64), but the Th2 cytokines IL-5, IL-6, and IL-10 also foster EAMG development (e.g., refs. [65][66][67]. The resistance to EAMG of mice genetically deficient in IL-6 is associated with a reduced formation of germinal centers in the spleen and a reduced synthesis of anti-AChR IgG Abs while the anti-AChR IgM response is normal, suggesting a defect in T cell help and in the switching from IgM to IgG isotypes (67).…”

Classical Complement Pathway in Experimental Autoimmune Myasthenia Gravis Pathogenesis

“…15 EAMG resistance is associated with reduced serum C1q, C3, or CIC levels in IL-6 knockout (KO), FcγRIII KO, CD59 KO, and IL-1 receptor antagonist-treated mice and with lower muscular C3 deposits in IFN-γ, IL-5, and ICOS KO mice. 7,9,[16][17][18][19] The first direct evidence for the role of complement system in EAMG came from studies showing that treatment of mice with complement-inhibiting reagents such as cobra venom factor (CVF), soluble complement receptor 1 (sCR1), and anti-C6 antibody prevents EAMG induced by passive transfer. [20][21][22] Likewise, following active immunization with AChRs in CFA, B10.D2/oSn (C5 deficient) mice demonstrated significantly reduced EAMG incidence/severity and muscle AChR loss as compared to B10.D2/nSn (C5 sufficient) mice.…”

“…IL-5 KO, IL-10 KO, FcγRIIb KO, FcγRIII KO, C4 KO, C5 deficient, and anti-C1q antibody-administered mice are partially or highly resistant to EAMG induction despite normal antibody and/or lymphocyte proliferation response to AChRs. 6,8,9,19,23,35 It is possible that the absence of certain genes or the consequential deficient production of cytokine/complements might reduce the ratios of high-affinity or complement-activating anti-AChR antibodies. In this case, despite significant anti-AChR antibody levels, NMJ destruction would be minimal, and therefore the severity of the clinical muscle weakness would be dampened.…”