Interleukin-6-deficient mice refractory to IgA dysregulation but not anorexia induction by vomitoxin (d eoxynivalenol) ingestion

Dietary exposure to the trichothecene vomitoxin (VT) causes feed refusal an d elevates IgA production in the mouse. Based on the observations that IL-6 can cause anorexia and promote IgA production and that gene expression of this cytokine is increased in vivo and ex vivo on VT exposure, we hypothesi zed that IL-6 is an essential cytokine in VT-induced feed refusal and IgA d ysregulation. To test this hypothesis, the effects of dietary VT on feed in take, weight gain, serum IgA levels and kidney mesangial IgA deposition in an IL-6-" knockout" mouse (B6129-IL6 (tmi Kopf)) were compared to those in both a corresponding " wild-type" (B6129F2) and a previously characterized " sentinel" strain (B6C3F1) that possess the intact gene for this cytokine. IL-6 deficiency did not alter the capacity of VT to cause feed refusal or impair weight gain. VT-fed B6129F2 and B6C3F1 mice had significantly higher serum IgA concentrations than did their corresponding controls fed clean d iet, whereas significant differences were not observed between IL-6 KO mice fed VT or control diets. Kidneys taken from VT-fed wild-type and sentinel mice had significantly increased mesangial IgA deposition as compared to co ntrols. While slight increases in mesangial IgA were observed in VT-fed IL- 6 KO mice, mean fluorescence intensities were significantly less than that found in the corresponding wild-type and sentinel strains. IL-6 KO mice app eared to be less prone to the development of microscopic haematuria followi ng VT exposure than were the corresponding wild-type and sentinel strains. In total, the results suggested that IL-6-deficient mice were refractory to VT-induced dysregulation of IgA production and development of IgA nephropa thy, whereas chronic VT-mediated nutritional effects related to feed intake and weight gain were unaffected. (C) 2000 Elseviev Science Ltd. All rights reserved.