Affiliation: Pharmacology Department, Jean Minjoz University Hospital, Bvd Fleming, F-25000 BESANCON,France.
Interleukin-10 (IL-10) is a cytokine with now well established immunomodulatory activity in both physiological and pathological processes. Its particular secretion pathway, i.e., a spontaneous production that increases after activation in many cell types, strengthens its regulatory role. Various drugs can interfere with the production of IL- 10, explaining, in part, their mechanism of action. This paper gives an overview of the effect of several major drugs on the production of IL-10 by various cell populations. Among glucocorticoids, dexamethasone is probably the most studied, and generally shows an inhibitory effect on the production of IL-10 in vitro. However, its effect depends on the type of stimulus and on its concentration, explaining probably some discrepant results reported in the literature. Interestingly, used in vivo, dexamethasone increased the plasmatic concentration of IL-10. Similar effects have been observed with methylprednisolone or hydrocortisone, as several clinical trials reported that these molecules induced an increase in IL-10 levels while, when used in vitro , these drugs led to a decrease in the production of IL-10. The other immunosuppressive drugs, such as tacrolimus or cyclosporin, inhibited the production of IL-10 by T- or B-lymphocytes. This effect seemed to be focused on these cells, that are the main targets of these drugs. This might explain why other models, such as peripheral blood mononuclear cells or whole blood are not sensitive to these drugs. In clinical trials, however, cyclosporin has also led to a decrease in IL-10 level. As well, the beta-adrenergic family appears to be one of the more interesting concerning its effect on IL-10 secretion. Indeed, epinephrine, norepinephrine, and beta agonists induced an increase in the production of IL-10 both in vitro and in vivo, while beta-blockers had the opposite effect. The use of beta2 selective agonists or antagonists has led to the attribution of such effect to beta2 receptors. The effects of other drugs, such as antihistamines, non-steroidal antiinflammatory drugs, gold derivatives, aprotinine, heparin, methotrexate, rituximab or OKT3 on the production of IL-10 will also be discussed in this review. Finally, the effects of various drugs on the production of IL-10 depend on several parameters. For instance, experiments performed in vivo or in vitro have sometimes led to opposite results. Interestingly, some drugs with so-called “wellknown” mechanisms of action have demonstrated more recently an effect on IL-10 secretion. As an example, adrenergic agonists such as epinephrine or beta2-agonists, have been shown to enhance the production of IL-10, an effect probably favorable when these drugs are used in asthma. Thus, some “old and well-known” drugs might in fact act in part through their ability to modulate the production of IL-10 at the local or general level. If such properties could be demonstrated, this could lead to a better knowledge of the mechanisms of the immunomodulatory properties of these drugs and to the design of new molecules targeting such secretions.