Sepsis-induced lung inflammation is modulated by insulin.
BACKGROUND
We have previously shown that diabetic rats are more susceptible to sepsis, but that the Acute lung injury (ALI) secondary to sepsis is less intense than in non-diabetics. In the present study, we further investigated the ALI-secondary to sepsis in diabetic rats and the effect of insulin treatment.


METHODS
Diabetes was induced in male Wistar rats by alloxan and sepsis by cecal ligation and puncture surgery (CLP). Some diabetic rats were given neutral protamine Hagedorn (NPH) insulin (4 IU, s.c.) 2 h before CLP. Six h later, the lungs were examined for edema, cell infiltration and prostaglandin-E2 (PGE2) levels in the bronchoalveolar lavage (BAL).


RESULTS
The results confirmed that leukocyte infiltration and edema were milder in diabetic rats with sepsis. After insulin treatment, the lung inflammation in diabetics increased to levels comparable to the non-diabetics. The BAL concentration of PGE2 was also lower in diabetics with sepsis, and increased after insulin treatment. Sepsis was followed by early fibroblast activation in the lung parenchyma, evaluated by increased transforming growth factor (TGF)-β and smooth muscle actin (α-SMA) expression, as well as an elevated number of cells with myofibroblasts morphology. These events were significantly lower in diabetic rats and increased after insulin treatment.


CONCLUSIONS
The results show that insulin modulates the early phase of inflammation and myofibroblast differentiation in diabetic rats.
Luciano Ribeiro
LR
Filgueiras
Vera L
VL
Capelozzi
Joilson O
JO
Martins
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. sojancar@icb.usp.br.
Sonia
S
Jancar
D000199:Actins / Q000378:metabolism; D055371:Acute Lung Injury / Q000382:microbiology / Q000473:pathology*; D000496:Alloxan; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D015232:Dinoprostone / Q000032:analysis; D004487:Edema / Q000382:microbiology*; D007328:Insulin / Q000627:therapeutic use*; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D058628:Myofibroblasts / Q000187:drug effects; D011014:Pneumonia / Q000382:microbiology / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000150:complications*; D013047:Specific Pathogen-Free Organisms; D016212:Transforming Growth Factor beta / Q000378:metabolism
D000199:Actins; D000496:Alloxan; D015232:Dinoprostone; D007328:Insulin; D016212:Transforming Growth Factor beta; C498862:Acta2 protein, rat