Acute generalized exanthematous pustulosis, a clue to neutrophil-mediated inflammatory processes orchestrated by T cells

PURPOSE OF REVIEW: Circumstantial evidence exists that certain neutrophilic inflammatory processes are regulated by T cells, but how this occurs is not well understood. The present review presents data on how T cells may directly orchestrate a neutrophilic inflammation by specific release of the neutrophil-attracting chemokine CXCL8 (formerly known as interleukin-8). RECENT FINDINGS: Acute generalized exanthematous pustulosis (AGEP) is an uncommon cutaneous eruption that is most often provoked by drugs, by acute infections with enteroviruses, or by mercury. It is characterized by acute, extensive formation of nonfollicular sterile pustules on an erythematous background, fever and elevated numbers of blood neutrophils. Involvement of T cells in drug-induced AGEP was suggested by positive patch tests and lymphocyte transformation tests. Moreover, drug-specific CD4+ and CD8+ T cells could be isolated and propagated in vitro from patch test sites and blood from AGEP patients. Their main characteristic is a high level of CXCL8 production. SUMMARY: T cells are involved even in some neutrophil-rich inflammatory responses, and they may orchestrate the immune reaction directly by high CXCL8 production or indirectly via interleukin-17 production, which induces CXCL8 production in various cell types. AGEP serves as a valuable model for characterizing T cells with a particular function--namely production of CXCL8--leading to neutrophilic inflammation. It is tempting to speculate that elucidation of this pathomechanism will help to improve our understanding of similar neutrophilic eruptions (e.g. pustular psoriasis) and may reveal new targets for pharmacotherapeutic interventions in such diseases.