Interleukin-10 and interleukin-4 have similar effects on hapten-specific primary antibody responses to penicillin in vivo.
Interleukin (IL)-10 was initially recognized on the basis of its capacity to inhibit production of interferon (IFN)-gamma by T helper (Th)1 lymphocytes; we examined whether this cytokine can bias the primary antibody (Ab) response to the hapten penicillin. We previously reported that BALB/c and SJL mice develop different responses to benzylpenicillin coupled to tetanus toxoid (BPO-TT). The response of SJL mice was characterized as Th2 on the basis of early and high IL-4 mRNA expression and production of BPO-specific Ab of the IgG1 isotype. In contrast, the response of BALB/c mice was characterized as Th1 on the basis of delayed and weaker IL-4 mRNA expression associated with high anti-BPO IgG2a production (Kerdine, S. et al., Mol. Immunol. 1996. 33: 71). In this report, we demonstrate that in naive animals, the level of expression of IL-10 mRNA in LN cells was high in SJL and barely detectable in BALB/c. In addition, injection of BPO-TT resulted in rapid and large increase of IL-10 mRNA expression in SJL. Neutralization of IL-10 in vivo promoted the production of BPO-specific IgG2a in SJL, and injection of IL-10-CHO cells inhibited BPO-specific IgG2a production in BALB/c. Neutralization on administration of IL-10 had effects very similar to neutralization or administration of IL-4. However, co-neutralization of IL-10 and IL-4 in SJL did not evidence additive or synergistic effects of the two cytokines. Administration of IL-10 or IL-4 in BALB/c inhibited BPO-TT-induced expression of IL-12 p40 mRNA without modulating IFN-gamma mRNA. Together, these data demonstrate that endogenous production of IL-10 regulates the production of IgG2a Ab in response to BPO-TT and that IL-10, like IL-4, is critical for controlling primary responses to antibiotics which behave as haptenic compounds.
Kerdine
S
S
Laboratoire d'Immunotoxicologie et de Cancérogenèse, Faculté de Pharmacie Paris Sud, Châtenay-Malabry, France.
Pallardy
M
M
Lamanètre
S
S
Bertoglio
J
J
Lebrec
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity / Q000187:drug effects*; D001667:Binding, Competitive / Q000276:immunology; D016466:CHO Cells; D006224:Cricetinae; D005260:Female; D006241:Haptens / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000187:drug effects* / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology* / Q000494:pharmacology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology* / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010400:Penicillin G / Q000276:immunology*; D013045:Species Specificity; D013745:Tetanus Toxoid / Q000276:immunology
D000911:Antibodies, Monoclonal; D006241:Haptens; D007074:Immunoglobulin G; D013745:Tetanus Toxoid; D016753:Interleukin-10; D015847:Interleukin-4; D010400:Penicillin G