Disruption of the IL-1beta gene diminishes acetylcholine   receptor-induced immune responses in a murine model of   myasthenia gravis.
Human autoimmune myasthenia gravis (MG) is associated with the IL-1beta TaqI RFLP allele 2. Individuals positive for this allele have high levels of inducible IL-1beta in their peripheral blood. Here, we have characterized MG induction and the immune response elicited by Torpedo acetylcholine receptor (AChR) immunization in wild-type and IL-1beta deficient (-/-) mice. Compared with wild-type mice, IL-1beta-/- mice were relatively resistant to induction of clinical experimental autoimmune myasthenia gravis (EAMG). Draining lymph node cells from IL-1beta-/- mice showed poor proliferative capacity upon AChR stimulation in vitro. Both Th1 (IFN-gamma, IL-2) and Th2 (IL-4) cytokine responses were reduced and levels of serum anti-AChR antibodies decreased in IL-1beta-/- mice compared to wild-type mice. Taken together, these results reveal a critical role for IL-1beta in the induction of MG in mice, and support a role for IL-1beta in the pathogenesis of MG in man.
Huang
D
D
Department of Neurosciences NC30, The Lerner ResearchInstitute, Cleveland Clinic Foundation, 9500-10000 Euclid Avenue, Cleveland, OH 44195, USA. huangd2@ccf.org
Shi
F D
FD
Giscombe
R
R
Zhou
Y
Y
Ljunggren
H G
HG
Lefvert
A K
AK
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D016207:Cytokines / Q000096:biosynthesis; D007114:Immunization; D007375:Interleukin-1 / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009157:Myasthenia Gravis / Q000209:etiology* / Q000276:immunology; D011950:Receptors, Cholinergic / Q000276:immunology*
D001323:Autoantibodies; D016207:Cytokines; D007375:Interleukin-1; D011950:Receptors, Cholinergic