title: Potential role of autoantibodies in the regulation of cytokine responses during bacterial infections.
abstract: An immunoregulatory mechanism involving release of neutralizing autoantibodies (Aabs) to self cytokines during bacterial infections is presented herein. Intraperitoneal inoculation of Haemophilus influenzae type b into Sprague-Dawley rats resulted in a self-limiting meningitis. High levels of cells expressing mRNA for gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) were detected 12 to 48 h postinoculation (p.i.) in splenocytes, and large numbers of IFN-gamma-secreting cells were present in the spleen on day 3 p.i. These levels were undetectable at days 9 and 14 p.i. Increased titers of Aabs of immunoglobulin G (IgG) isotypes to both cytokines were observed, with a peak at day 7 p.i. and with very low levels at day 30. Upon reinoculation with H. influenzae type b at day 30, regeneration of Aabs was recorded 7 days later (i.e., at day 37). To elucidate their regulatory importance, Aabs dose-dependently inhibited IFN-gamma production by splenocytes, IFN-gamma-induced major histocompatibility complex expression by peritoneal macrophages, and TNF-alpha-induced thymocyte proliferation. To control the specificity of these Aabs, Fab fragments of purified serum Igs from day p.i. exhibited binding and neutralizing effects. Furthermore, preincubation of the sera with a cytokine inhibited the binding and neutralization effects of that particular cytokine, but not those of any other cytokine. Aab-producing B cells were cloned, and their supernatants had similar effects. Our data suggest a role for autoimmunity in cytokine regulation and suggest that a maintained balance of this mechanism may protect from sequelae.
authors.affiliation: Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden. Moiz.Bakhiet@cnsf.ki.se
authors.forename: M
authors.initials: M
authors.lastname: Bakhiet
authors.forename: A
authors.initials: A
authors.lastname: Diab
authors.lastname: Mahamustafa
authors.lastname: Jiezhu
authors.forename: L
authors.initials: L
authors.lastname: Lindqvist
authors.forename: H
authors.initials: H
authors.lastname: Link
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000502:physiology*; D006192:Haemophilus Infections / Q000276:immunology*; D006193:Haemophilus influenzae; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology
chemical_list: D001323:Autoantibodies; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma