Pretreatment of mice with lipopolysaccharide (LPS) or IL-1beta exerts dose-dependent opposite effects on Shiga toxin-2 lethality.
Haemolytic uraemic syndrome (HUS) has been closely associated with infection with a group of Shiga toxin-producing enterohaemorrhagic Eschericchia coli in young children. Shiga toxins (Stx) have been implicated as pathogenic agents of HUS by binding to the surface receptor of endothelial cells. LPS is a central product of the Gram-negative bacteria and several reports have documented that both LPS and Stx are important for disease development. In this study the reciprocal interactions between LPS and Stx2 are analysed in a mouse model. The results demonstrated that LPS was able to reduce or enhance Stx2 toxicity, depending on the dose and the timing of the injection. The involvement of the main early cytokines induced by LPS, tumour necrosis factor alpha (TNF-alpha) and IL-1beta, in those LPS opposite effects on Stx2 toxicity was evaluated. Stx2 toxicity was enhanced by in vivo injection of murine TNF-alpha and low doses of murine IL-1beta. However, at higher doses of IL-1beta which induced corticosteroid increase in serum, Stx2 lethality was decreased. Considering that dexamethasone and IL-1beta reproduce the LPS protective effects, it is suggested that endogenous corticosteroids secondary to the inflammatory response induced by LPS, mediate the protection against Stx2. It can be concluded that the fine equilibrium between proinflammatory and anti-inflammatory activities strongly influences Stx2 toxicity.
Palermo
M
M
División Inmunología, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Infecciosas, ANLIS, Buenos Aires, Argentina. PALERMO@ANMRA.SLD.AR
Alves-Rosa
F
F
Rubel
C
C
Fernández
G C
GC
Fernández-Alonso
G
G
Alberto
F
F
Rivas
M
M
Isturiz
M
M
D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D002648:Child; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D004926:Escherichia coli / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000209:etiology / Q000276:immunology; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000097:blood / Q000209:etiology* / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000008:administration & dosage; D007375:Interleukin-1 / Q000008:administration & dosage*; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000008:administration & dosage; D022603:Shiga Toxins; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
D001427:Bacterial Toxins; D018836:Inflammation Mediators; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D022603:Shiga Toxins; D014409:Tumor Necrosis Factor-alpha; D003345:Corticosterone