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Thymulin Inhibits Monocrotaline-Induced Pulmonary Hypertension Modulating Interleukin-6 Expression and Suppressing p38 Pathway

Department of Physiology (T.H.-C., S.M.O., R.R.-A., A.L.N., M.S., F.L.F.C., A.B.-N., A.F.L.-M.), Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; and Life and Health Sciences Research Institute (ICVS) (R.S.M., C.N.-S., J.C.-P.), School of Health Sciences, University of Minho, 4704-553 Braga, Portugal

Address all correspondence and requests for reprints to: Professor Adelino F. Leite-Moreira, Department of Physiology, Faculty of Medicine, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal. E-mail: amoreira{at}med.up.pt.

The pathogenesis of pulmonary hypertension (PH) includes an inflammatory response. Thymulin, a zinc-dependent thymic hormone, has important immunobiological effects by inhibiting various proinflammatory cytokines and chemokines. We investigated morphological and hemodynamic effects of thymulin administration in a rat model of monocrotaline (MCT)-induced PH, as well as the pattern of proinflammatory cytokine gene expression and the intracellular pathways involved. Adult Wistar rats received an injection of MCT (60 mg/kg, sc) or an equal volume of saline. One day after, the animals randomly received during 3 wk an injection of saline, vehicle (zinc plus carboxymethyl cellulose), or thymulin (100 ng/kg, sc, daily). At d 23–25, the animals were anesthetized for hemodynamic recordings, whereas heart and lungs were collected for morphometric and molecular analysis. Thymulin prevented morphological, hemodynamic, and inflammatory cardiopulmonary profile characteristic of MCT-induced PH, whereas part of these effects were also observed in MCT-treated animals injected with the thymulin’s vehicle containing zinc. The pulmonary thymulin effect was likely mediated through suppression of p38 pathway.