title: Interleukin-10 regulates quartz-induced pulmonary inflammation in rats.
abstract: Interleukin-10 (IL-10) can downregulate expression of several proinflammatory cytokines including chemokines. This study investigated the role of IL-10 in the acute response of the rat lung to quartz particles. Intratracheal instillation of rats with 1 mg of quartz produced an inflammatory and cytotoxic response demonstrated by increased bronchoalveolar lavage (BAL) fluid neutrophils, lactate dehydrogenase, and protein. IL-10 was detected in rat lung, but IL-10 levels were not altered by quartz. In contrast, quartz increased lung levels of the chemokine macrophage inflammatory protein-2 (MIP-2). Treatment with recombinant murine IL-10 (rmIL-10) attenuated quartz-induced pulmonary inflammation and injury. Pretreatment with anti-IL-10 antiserum enhanced inflammatory responses to quartz. Consistent with effects on quartz-induced inflammation, rmIL-10 and anti-IL-10 serum decreased and increased, respectively, lung MIP-2 mRNA and protein in response to quartz. Additionally, rmIL-10 reduced production of hydrogen peroxide, superoxide anion, and nitric oxide by BAL cells from quartz-exposed and control rats. These results demonstrate that IL-10 is expressed in rat lung and downregulates quartz-induced inflammation and cell activation. The mechanism of the anti-inflammatory action of IL-10 after quartz administration involves, at least in part, attenuation of MIP-2 expression.
authors.affiliation: The Procter & Gamble Company, Cincinnati, Ohio 45253, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Driscoll
authors.forename: J M
authors.initials: JM
authors.lastname: Carter
authors.forename: B W
authors.initials: BW
authors.lastname: Howard
authors.forename: D
authors.initials: D
authors.lastname: Hassenbein
authors.forename: M
authors.initials: M
authors.lastname: Burdick
authors.forename: S L
authors.initials: SL
authors.lastname: Kunkel
authors.forename: R M
authors.initials: RM
authors.lastname: Strieter
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D054426:Chemokine CXCL2; D002630:Chemotactic Factors / Q000096:biosynthesis / Q000235:genetics; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D016753:Interleukin-10 / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008297:Male; D015846:Monokines / Q000096:biosynthesis / Q000235:genetics*; D011791:Quartz / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D000906:Antibodies; D054426:Chemokine CXCL2; D002630:Chemotactic Factors; D015846:Monokines; D011994:Recombinant Proteins; D016753:Interleukin-10; D011791:Quartz