THE EFFECT OF CYTOKINES ON BACTERICIDAL ACTIVITY OF MURINE NEUTROPHILS

A range of recombinant cytokines have now been shown to modify aspects of the phenotype and function of human and murine neutrophils. Howeve r, few reports describe modification of the bactericidal activity of n eutrophils. We therefore examined the recombinant murine cytokines tum or necrosis factor-alpha (TNF-alpha, 10-1000 ng ml(-1)) and granulocyt e macrophage-colony stimulating factor (GM-CSF, 10-1000 U ml(-1)) for their ability to increase the bacterial killing capacity of murine neu trophils. Neutrophils from either bone marrow (fresh or cultured), or peritoneal exudates, or abscesses, were pre-incubated with either cyto kine for 30-60 min and the killing of Proteus mirabilis, Escherichia c oli, or Bacteroidrs fragilis was examined in the presence or absence o f serum over a 90 min period. Only for one combination was a small but significantly enhanced level of bacteria killing observed, the phagoc ytic killing of P. mirabilis by peritoneal exudate neutrophils in the presence of GM-CSF and serum. With this exception there was no enhance ment of bacterial killing for the range of combinations of neutrophils and bacterial species tested. In contrast, at the concentrations test ed for effect on bactericidal activity, TNF-alpha and GM-CSF were able to significantly upregulate CR3 (but not Fc gamma RII) expression on mouse neutrophils. These results indicate that upregulation of CR3 as an index of neutrophil activation does not necessarily correlate with increased bactericidal activity.