Monocrotaline induces interleukin-6 mRNA expression in rat lungs.
Monocrotaline-induced pulmonary hypertension (PH) in rats is preceded by an inflammatory response in the lungs, and interleukin-6 (IL-6) is expressed in response to inflammation. To evaluate the role of IL-6 in monocrotaline-induced PH, rats received a single subcutaneous injection of monocrotaline (60 mg/kg) or an equivalent amount of normal saline. Pulmonary artery pressure (Ppa), right ventricular hypertrophy (RVH), expression of IL-6 mRNA, and bioactivity of IL-6 in the lungs of these rats were examined 48 hours and 1 and 2 weeks after administration of monocrotaline. The effects of dexamethasone treatment on monocrotaline-induced PH also were evaluated. Two weeks after administration of monocrotaline, significant PH and RVH developed in these rats. Reverse transcription-polymerase chain reaction (RT-PCR) revealed expression of IL-6 mRNA in the lungs 48 hours and 1 and 2 weeks after administration of monocrotaline. This was confirmed using ribonuclease protection assay. The bioactivity of IL-6 in lung extracts progressively increased. Dexamethasone markedly inhibited expression of IL-6 mRNA and IL-6 bioactivity in the lungs, with concomitant attenuation of monocrotaline-induced PH and RVH. Our data show that monocrotaline induces expression of IL-6 mRNA in rat lungs and that inhibition of IL-6 results in attenuation of PH. These findings indicate that IL-6 may play a role in the pathogenesis of PH.
Bhargava
A
A
Department of Pathology, New York Medical College, Valhalla, New York 10595, USA.
Kumar
A
A
Yuan
N
N
Gewitz
M H
MH
Mathew
R
R
D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003907:Dexamethasone / Q000627:therapeutic use*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000378:metabolism*; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016686:Monocrotaline; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D012333:RNA, Messenger; D016686:Monocrotaline; D003907:Dexamethasone