Leptin treatment ameliorates acute lung injury in rats with cerulein-induced acute pancreatitis.
OBJECTIVE
To determine the effect of exogenous leptin on acute lung injury (ALI) in cerulein-induced acute pancreatitis (AP).


METHODS
Forty-eight rats were randomly divided into 3 groups. AP was induced by intraperitoneal (i.p.) injection of cerulein (50 microg/kg) four times, at 1 h intervals. The rats received a single i.p. injection of 10 mug/kg leptin (leptin group) or 2 mL saline (AP group) after cerulein injections. In the sham group, animals were given a single i.p. injection of 2 mL saline. Experimental samples were collected for biochemical and histological evaluations at 24 h and 48 h after the induction of AP or saline administration. Blood samples were obtained for the determination of amylase, lipase, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, macrophage inflammatory peptide (MIP)-2 and soluble intercellular adhesion molecule (sICAM)-1 levels, while pancreatic and lung tissues were removed for myeloperoxidase (MPO) activity, nitric oxide (NOx) level, CD40 expression and histological evaluation.


RESULTS
Cerulein injection caused severe AP, confirmed by an increase in serum amylase and lipase levels, histopathological findings of severe AP, and pancreatic MPO activity, compared to the values obtained in the sham group. In the leptin group, serum levels of MIP-2, sICMA-1, TNF-alpha, and IL-1beta, pancreatic MPO activity, CD40 expression in pancreas and lung tissues, and NOx level in the lung tissue were lower compared to those in the AP group. Histologically, pancreatic and lung damage was less severe following leptin administration.


CONCLUSIONS
Exogenous leptin attenuates inflamma-tory changes, and reduces pro-inflammatory cytokines, nitric oxide levels, and CD40 expression in cerulein-induced AP and may be protective in AP associated ALI.
Gultekin
Fatma Ayca
FA
Gazi University, School of Medicine, Department of General Surgery, Besevler 06510 Ankara, Turkey. faycagultekin@yahoo.com
Kerem
Mustafa
M
Tatlicioglu
Ertan
E
Aricioglu
Aysel
A
Unsal
Cigdem
C
Bukan
Neslihan
N
D000208:Acute Disease; D000818:Animals; D019013:CD40 Antigens / Q000378:metabolism; D002108:Ceruletide; D054426:Chemokine CXCL2; D019743:Chemokines, CXC / Q000097:blood; D005260:Female; D053583:Interleukin-1beta / Q000097:blood; D020738:Leptin / Q000627:therapeutic use*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000150:complications*; D009195:Peroxidase / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D019013:CD40 Antigens; D054426:Chemokine CXCL2; D019743:Chemokines, CXC; C513296:Cxcl2 protein, rat; D053583:Interleukin-1beta; D020738:Leptin; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D002108:Ceruletide; D009195:Peroxidase