THE EFFECT OF INTERLEUKIN-8 AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR ON THE RESPONSE OF NEUTROPHILS TO FORMYL-METHIONYL-LEUCYL-PHENYLALANINE

Neutrophils isolated from patients with chronic bronchitis and emphyse ma have been shown to have enhanced responses to formyl peptides when assessed in vitro compared to age, sex matched controls. It is current ly unclear whether the observed differences are due to a 'priming' eff ect by a second agent in vivo, or whether this is a primary difference in the neutrophils, We have studied the effects of interleukin-8, whi ch is thought to be one of the major pro-inflammatory cytokines in chr onic lung disease and granulocyte macrophage colony stimulating factor (GMCSF, in order to assess their effects on neutrophil chemotaxis and connective tissue degradation. In addition, we have assessed the effe ct of preincubation of these agents with neutrophils for 30 min follow ed by stimulation with F-Met-Leu-Phe (FMLP) to investigate any possibl e 'priming' effect that may he relevant to our clinical data. We repor t suppression of neutrophil chemotaxis to FMLP following incubation of the neutrophils with both IL-8 and GMCSF. However, we have observed a n additive effect of IL-8 and FMLP for neutrophil degranulation leadin g to fibronectin degradation. The results suggest that IL-8 does not ' prime' neutrophils for subsequent FMLP stimulation as observed in vivo . Although the results for GMCSF were similar for the chemotactic resp onse, the agent also had a synergistic effect on connective tissue deg radation. However, it is concluded that neither agent could explain th e enhanced neutrophil responses seen in our patients. (C) 1998 Elsevie r Science B.V. All rights reserved.