RESUMO
Although different populations of inflammatory cells infiltrate the healing wound, the mechanisms by which they influence the healing process in vivo are poorly defined. In vitro studies suggest that these cells may mediate wound healing by releasing various cytokines within the wound. We measured the levels of interleukin (IL) 1, IL-2, IL-3, IL-4, IL-6, tumor necrosis factor, and macrophage colony-stimulating factor within a subcutaneously implanted polyurethane sponge on various days after injury. Significantly higher levels of IL-1, IL-6, tumor necrosis factor, and macrophage colony-stimulating factor were detected in the wound fluid compared with basal serum levels in nonwounded mice. Tumor necrosis factor, macrophage colony-stimulating factor, and IL-6 peaked earlier than IL-1; however, the levels of these cytokines had fallen by the 13th day after wounding. Interleukin 2, IL-3, and IL-4 could not be detected in the wound fluid, and the wound fluid inhibited the proliferation of the IL-2-dependent cell lines CTLL-2 and HT-2 in response to recombinant IL-2. We hypothesize that tumor necrosis factor, macrophage colony-stimulating factor, IL-1, and IL-6, which are secreted at the site of injury, interact to promote tissue remodeling. The decrease in the levels of these cytokines by the 13th day after wounding may be the result of a regulatory process by the healed wound.
Assuntos
Fatores Biológicos/biossíntese , Cicatrização , Animais , Ensaio de Unidades Formadoras de Colônias , Fatores Estimuladores de Colônias/biossíntese , Citocinas , Feminino , Interleucina-1/biossíntese , Interleucina-2/biossíntese , Interleucina-4/biossíntese , Interleucina-6/biossíntese , Fator Estimulador de Colônias de Macrófagos , Camundongos , Camundongos Endogâmicos BALB C , Poliuretanos , Fator de Necrose Tumoral alfa/biossíntese , Ferimentos e Lesões/etiologia , Ferimentos e Lesões/metabolismoRESUMO
Patients with refractory carcinoma were treated with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) by intravenous (IV) infusion. During the period of treatment, studies of polymorphonuclear leukocyte superoxide (O2-) release in response to formylmethionylleucylphenylalanine (fMLP) and phorbol myristate acetate (PMA) and studies of chemotaxis in response to fMLP and C5a were performed. We observed that patients receiving rhGM-CSF in vivo exhibited primed O2- release after stimulation both with fMLP and PMA. Chemotaxis, however, was not enhanced by the treatment. These data suggest that host defenses may be enhanced by this treatment and that rhGM-CSF may be a useful therapeutic adjunct in compromised patients.