Custom Search


Friday 01 November 2002

The beta 2-adrenergic agonist salbutamol potentiates oral induction of tolerance, suppressing adjuvant arthritis and antigen-specific immunity.

By: Cobelens PM, Kavelaars A, Vroon A, Ringeling M, van der Zee R, van Eden W, Heijnen CJ.

J Immunol 2002 Nov 1;169(9):5028-35

Therapeutic protocols for treating autoimmune diseases by feeding autoantigens during the disease process have not been very successful to date. In vitro it has been shown that beta-adrenergic agonists inhibit pro-inflammatory cytokine production and up-regulate anti-inflammatory cytokine production. We hypothesized that the protective effect of oral administration of Ag would be enhanced by oral coadministration of the beta(2)-adrenergic agonist salbutamol. Here we demonstrate that oral administration of salbutamol in combination with the Ag mycobacterial 65-kDa heat shock protein increased the efficacy of disease-suppressive tolerance induction in rat adjuvant arthritis. To study the mechanism of salbutamol in more detail, we also tested oral administration of salbutamol in an OVA tolerance model in BALB/c mice. Oral coadministration of OVA/salbutamol after immunization with OVA efficiently suppressed both cellular and humoral responses to OVA. Coadministration of salbutamol was associated with an immediate increase in IL-10, TGF-beta, and IL-1R antagonist in the intestine. The tolerizing effect of salbutamol/OVA was maintained for at least 12 wk. At this time point IFN-gamma production in Ag-stimulated splenocytes was increased in the OVA/salbutamol-treated animals. In conclusion, salbutamol can be of great clinical benefit for the treatment of autoimmune diseases by promoting oral tolerance induction.

Use of this site is subject to the following terms of use