Immunomodulatory role of thymulin in lung diseases.
BACKGROUND
Inflammation is a hallmark of lung diseases. The available treatment options are unsatisfactory because they are not efficacious or induce major side effects. Alternative approaches need to be developed. Thymulin is a peptide exclusively produced in the thymus with several anti-inflammatory properties.


METHODS
The physiological features of thymulin and data that support its potential as an anti-inflammatory treatment for lung diseases are reviewed.


RESULTS
Thymulin has consistent beneficial effects in experimental models of lung diseases. It has a broad inhibitory effect on pro-inflammatory cytokines, suppresses p38 (a MAPK family member) and inhibits the activation of the NF-kappaB signal pathway. It is an attractive peptide for lung gene therapy because has no toxicity even at high doses and when expressed by adenoviral vectors reduces immune response against viral proteins.


CONCLUSIONS
Thymulin has a selective immunomodulatory effect, enhancing anti-inflammatory and inhibiting pro-inflammatory cytokines. It suppresses p38 (implicated in glucocorticoid-resistance) and inhibits NF-kappaB activation, which has an important pathogenic role in several lung diseases. The broad spectrum of anti-inflammatory effects of this peptide in several animal models of lung disease makes thymulin a good candidate for future clinical trials.
Santos
Mário
M
University of Porto, Department of Physiology, Cardiovascular R&D Unit, Faculty of Medicine, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal.
Henriques-Coelho
Tiago
T
Leite-Moreira
Adelino
A
D000818:Animals; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007249:Inflammation / Q000150:complications / Q000378:metabolism; D008171:Lung Diseases / Q000188:drug therapy* / Q000209:etiology; D015398:Signal Transduction / Q000502:physiology; D013935:Thymic Factor, Circulating / Q000737:chemistry / Q000502:physiology / Q000627:therapeutic use*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
D007155:Immunologic Factors; D013935:Thymic Factor, Circulating; D048051:p38 Mitogen-Activated Protein Kinases