1. ¹Laboratoire d'Immunologie et Unité INSERM 479, Hôpital Bichat, Paris, France
2. ²Département d'Anesthésie-Réanimation, Hôpital Saint-Louis, Paris, France
3. ³Service de Biochimie Hormonale et Génétique, Hôpital Bichat, Paris, France
4. ⁴Service de Biochimie A et Unité INSERM 408, Hôpital Bichat, Paris, France

Correspondence: Dr S Chollet-Martin, PhD, Laboratoire d'Immunologie et Unité INSERM 479, Hôpital Bichat, 46 rue Henri Huchard, 75018 Paris, France. E-mail: sylvie.martin@bch.ap-hop-paris.fr

Received 22 January 2004; Revised 6 May 2004; Accepted 10 May 2004; Published online 28 June 2004.

Abstract

Interferon (IFN) is a Th1 cytokine mainly produced by T cells, NK cells and macrophages in response to interleukin (IL)-12. As polymorphonuclear neutrophils (PMN) have been shown to produce and to release numerous cytokines, in particular upon IL-12 stimulation, we investigated the ability of highly purified PMN to secrete IFN. We found that PMN contained a small store of IFN, and that this store was rapidly secreted upon stimulation by degranulating agents such as formyl peptides. Moreover, after a few hours of stimulation with appropriate agents, PMN synthesized IFN. The effect of IL-12 was time- and concentration-dependent, and IL-12 combinations with IL-2, IL-15, IL-18 or LPS were highly synergistic. Cycloheximide inhibited IFN release in such optimal conditions, confirming the ability of PMN to synthesize IFN. IFN synthesis was associated with an increase in specific mRNA content, pointing to a transcriptional mechanism. The IFN produced by PMN was biologically active, as demonstrated by its ability to induce TNF synthesis by PMN themselves or to induce IL-10 synthesis by peripheral blood mononuclear cells. These findings reveal a novel pathway of autocrine and paracrine PMN activation. They also identified a new role for IFN, bridging innate and adaptive immune responses.