Local administration of interleukin-1beta for the treatment of lung abscesses induces neutrophil activation and changes in proinflammation cytokine production.
Interleukin-1 (IL-1) is a potent immunostimulatory molecule with broad range biological activity that limits its systemic application in humans. Alternatively, IL-1 can be applied locally, directly to the inflammatory site for stimulation of local defense mechanisms, without activating an acute phase response. IL-1beta preparations have been successfully used for local therapy of patients with purulent bacterial lung abscesses who were resistant to usual antibiotic treatment. IL-1beta was applied directly to the abscess cavity at a concentration of 10 ng/ml, once a day for 7 days. Before IL-1beta administration, local leukocyte functional activity was significantly reduced compared to the same activity in neutrophils isolated from the peripheral blood of the same patient. Local application of IL-1beta led to increases in adhesion, chemotaxis, oxygen radical production and phagocytosis of abscess fluid neutrophils. After local IL-1beta treatment, the concentration of IL-8 and TNF-alpha in the abscess fluids increased, while in nearly all patients levels of endogenous IL-1beta decreased. Immunocytochemical analysis showed that IL-1beta increased the numbers of cytokine-producing cells and induced proinflammatory cytokine production by neutrophilic granulocytes. According to the results obtained, the mechanism of the local immunostimulatory activity by IL-1beta is associated with the significant activation of neutrophilic granulocyte functions and changes in cytokine production at the inflammatory site. IL-1beta can be used as a highly effective immunotherapeutic drug when applied locally at adequate immunostimulatory dose levels.
Simbirtsev
A
A
Institute of Highly Pure Biopreparations, Pudozhskaya st.,7, St. Petersburg, 197110, Russia. sim@inshpb.spb.su
Variouchina
E
E
Konusova
V
V
Kotov
A
A
Ketlinsky
S
S
Salamatov
A
A
Bisenkov
L
L
D000328:Adult; D000368:Aged; D001999:Bronchoscopy; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects; D005122:Exudates and Transudates / Q000737:chemistry; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007249:Inflammation / Q000276:immunology*; D015552:Injections, Intralesional; D007375:Interleukin-1 / Q000008:administration & dosage* / Q000032:analysis; D016209:Interleukin-8 / Q000819:agonists; D008169:Lung Abscess / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000819:agonists
D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha