The effects of IL-10 on proinflammatory cytokine expression (IL-1beta and IL-8) in hyaline membrane disease (HMD).
Deficient expression of the counterregulatory cytokine IL-10 by lung inflammatory cells may facilitate chronic inflammation and the pathogenesis of hyaline membrane disease (HMD), in premature infants. To determine if pathways which regulate proinflammatory cytokines in response to human recombinant IL-10 (rIL-10) were functional in the lungs of these neonates, bronchoalveolar lavage (BAL)-derived lung inflammatory cells (predominantly macrophages and neutrophils) from infants with HMD were cultured in the presence of lipopolysaccharide (LPS) and increasing concentrations of (rIL-10). The expression of IL-1beta and IL-8 protein was assessed 24 h later. IL-10 protein was also measured from the BAL aspirates of these newborns at 4-day intervals over the first month of life. In cell culture IL-1beta expression was inhibited by rIL-10 in a dose-dependent fashion while IL-8 expression was inhibited by higher concentrations of rIL-10. IL-10 protein was undetectable from BAL fluid of the premature infants sampled over 28 days. The results demonstrate that lung inflammatory cells, which do not express IL-10 in vivo, are capable of responding to rIL-10 in cell culture with reduction of IL-1beta and IL-8 expression. These data support the rationale for the development of rIL-10 as a potential anti-inflammatory agent in the treatment of HMD.
Department of Pediatrics, Women's and Children's Hospital, Los Angeles, California, 90033, USA. kkwong@pol.net
K Y
KY
Kwong
C A
CA
Jones
R
R
Cayabyab
C
C
Lecart
N
N
Khuu
I
I
Rhandhawa
J M
JM
Hanley
R
R
Ramanathan
R A
RA
deLemos
P
P
Minoo
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006819:Hyaline Membrane Disease / Q000209:etiology / Q000276:immunology* / Q000628:therapy; D066298:In Vitro Techniques; D007231:Infant, Newborn; D018836:Inflammation Mediators / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D000894:Anti-Inflammatory Agents, Non-Steroidal; C507763:IL1RN protein, human; D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10