Predominant inhibition of Th1 cytokines in New Zealand black/white F1 mice treated with FK506

Abstract

The T-helper 1/T-helper 2 (Th1/Th2) cell balance was examined in 6-month-old New Zealand black/white F1 (B/WF1) mice treated with an immunosuppressive agent, FK506. The survival rate of mice treated with 10 mg/kg/day of FK506 was 7/8, while that of those treated with 2.5 mg/kg/day was 5/8, and 4/8 after treatment for 8 weeks with placebo. Proteinuria, which was already positive in all mice before the treatment, in the seven of eight mice treated with 10 mg/kg/day remained mildly positive (< or = 1+), while seven of eight mice treated with 2.5 mg/kg/day and six of eight mice treated with the placebo showed severe proteinuria (> or = 2+). Pathological changes in the kidneys of mice treated with 10 mg/kg/day of FK506 were less severe than in mice treated with the placebo or 2.5 mg/kg/day of FK506. Expression of mRNA was unchanged for all cytokines determined in the groups treated with 2.5 mg/kg/day of FK506 or placebo. In contrast, expression of mRNA for interleukin (IL)-2, and interferon (IFN)-gamma was suppressed, while that for IL-4 and IL-10 was not suppressed in the group treated with 10 mg/kg of FK506. The serum levels of IgG-class anti-DNA antibodies, which had been elevated before the treatment, were suppressed--especially in the IgG2a subclass--and the deposition of IgG2a and IgG2b in the glomeruli was reduced in the group treated with 10 mg/kg/day of FK506 compared with the other groups. These findings suggest that an improvement in the lupus nephritis of 6-month-old B/WF1 mice induced by FK506 might be associated with a predominant inhibition of Th1 cytokine.

Factors associated with severe versus mild immunotherapy-related systemic reactions: A case-referent study

“…6 This drug is known to affect the intestinal barrier, increasing permeability for allergenic food proteins, 2 and has been shown to induce a shift toward a T H 2 profile of cytokine and IgE production. 8,9 In our study increased total and specific IgE levels were observed in allergic patients but not in the control group, except in 1 control patient for total IgE. Tacrolimus-treated patients have an increased intestinal permeability and significantly higher serum LPS/endotoxin levels compared with healthy volunteers.…”

The constant region affects antigen binding of antibodies to DNA by altering secondary structure

“…Abs both to DNA and histone are believed to be important in the pathogenesis of SLE (Muller et al, 2008; Kiss et al, 2009; Cohen-Solal and Diamond, 2011; Pavlovic et al, 2011), and at least for pathogenic anti-DNA Abs there is a bias towards Abs of the IgG2a and IgG3 isotypes (Sugiyama et al, 2004; Baudino et al, 2006; Mannoor et al 2012; Moser et al, 2012). It is important to note that variations in binding between PL9-11 switch variants were not only related to C region differences, but also to the properties of the Ag studied.…”

Selective Sequestration of STAT1 in the Cytoplasm via Phosphorylated SHP-2 Ameliorates Murine Experimental Colitis

“…1D). Cyclosporin A and FK506 inhibited both the Th1 and Th2 immune responses (49)(50)(51). Fusaruside showed a significant resolution of TNBS-induced colitis in mice by inhibiting IFN-g/STAT1/T-bet signaling (Fig.…”