Low-Molecular-Weight Heparin and Unfractionated Heparin Decrease Th-1, 2, and 17 Expressions

Abstract

BackgroundWe evaluated the effects of T helper cell differentiation in a mite-allergic animal model treated with inhaled heparins of different molecular weight.MethodBALB/c mice were divided into four groups: 1. Control, 2. Mite intratracheal (mIT), 3. Inhaled heparin (hIN), 4. Inhaled low-molecular-weight heparin (lmwhIN). Groups 2, 3, and 4 were sensitized twice with Der p allergen subcutaneously on day 1 and day 8. Der p allergen was administered intratracheally on day 15. Groups 3 and 4 were treated with heparin or low-molecular-weight (lmw) heparin intranasally from day 1 to 22. Splenocytes from sacrificed mice stimulated with 16 µg/ml of Der p were cultured for 72 hours. Supernatants of splenocyte were collected to analyze the effect of Interleukin (IL)17-A/F, Interferon(IFN)-γ, IL-4, IL-13, and IL-10. Serum was also collected for Der P-specific IgE level on day 23. Total RNA was extracted from spleen tissue for mRNA expression. Gene expression of Foxp3, IL-10 IFN-γ, GATA3, IL-5, and RORγt were analyzed.ResultsBoth hIN and lmwhIN groups had lower serum IgE level than that of the mIT group (both p<0.0001). Both hIN and lmwhIN groups showed significantly decreased transcripts of GATA-3, IFN-γ, IL-5, and RORγt mRNA in their spleen. Regarding the supernatant of splenocyte culture stimulated with Der p, compared with the mIT group, there were significant decreases in IL-17A/F, IFN-γ, IL-4, IL-13, and IL-10 secretion in inhaled hIN and lmwhIN groups.ConclusionsFrom this balb/c mice study, the analyses of mRNA and cytokines revealed that both intranasal heparin and lmw heparin treatment decreased the expression of Th1, Th2, and Th17 in spleen. The underlying mechanism(s) warrant further studies.

Sulfated non-anticoagulant heparin blocks Th2-induced asthma by modulating the IL-4/signal transducer and activator of transcription 6/Janus kinase 1 pathway

“…The effect on GATA-3 may in turn explain the simultaneous effects of S-NACH treatment on IL-4, IL-5, and IL-13 in mice acutely or chronically challenged with OVA. These results are consistent with those reported by Huang et al [ 26 ] using a house dust mite extract-based model of asthma. Unlike that study, which reported a modulatory effect of LMWH on both Th1 and Th2 cytokines, our study showed that S-NACH was more selective against Th2 cytokines because it did not affect IFNγ levels after OVA exposure either acutely or chronically.…”

Heparin affects the induction of regulatory T cells independent of anti-coagulant activity and suppresses allogeneic immune responses

“…Several studies have shown that heparin has inhibitory effects on T cell proliferation in MLRs [4,38] and natural killer cell cytotoxicity [39]. Reduced differentiation of Th1, Th2, and Th17 in the spleen by both heparin and LMWH treatment has also been reported [40]. The results of these studies support the hypothesis that heparin promotes T reg induction.…”

Non-anticoagulant derivatives of heparin for the management of asthma: distant dream or close reality?

“…As necrosis factor-alpha [145,190,234]. However, the current study for the first time demonstrated that enoxaparin can significantly inhibit the release of IL-6 and IL-8 from the stimulated lung epithelial cells.…”