Interleukin-6-deficient mice refractory to IgA dysregulation but not anorexia induction by vomitoxin (deoxynivalenol) ingestion.
Dietary exposure to the trichothecene vomitoxin (VT) causes feed refusal and 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 hypothesized that IL-6 is an essential cytokine in VT-induced feed refusal and IgA dysregulation. To test this hypothesis, the effects of dietary VT on feed intake, 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 "wildtype" (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 diet, 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 controls. 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 appeared to be less prone to the development of microscopic haematuria following 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 nephropathy, whereas chronic VT-mediated nutritional effects related to feed intake and weight gain were unaffected.
Pestka
J J
JJ
Dept of Food Science and Human Nutrition, Michigan State University, East Lansing 48824, USA. pestka@pilot.msu.edu
Zhou
H R
HR
D000818:Animals; D000855:Anorexia / Q000097:blood / Q000139:chemically induced* / Q000652:urine; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D005920:Glomerular Mesangium / Q000276:immunology; D005921:Glomerulonephritis / Q000139:chemically induced; D006417:Hematuria / Q000139:chemically induced; D007070:Immunoglobulin A / Q000096:biosynthesis* / Q000097:blood; D015850:Interleukin-6 / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D014255:Trichothecenes
D007070:Immunoglobulin A; D015850:Interleukin-6; D014255:Trichothecenes; C007262:deoxynivalenol