Address for correspondence: Wilson Savino, Laboratory on Thymus Research, Department of Immunology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Ave. Brasil 4365, Manguinhos 21045-900 - Rio de Janeiro, Brazil. Voice: 55 21 2588-4557; fax: 55 21 2280 1589.
savino{at}gene.dbbm.fiocruz.br
Ann. N.Y. Acad. Sci. 992: 179-185 (2003).
Increasing evidence has placed the thymus as a target for neuroendocrine
control. Herein we review the pleiotropic effects of growth
hormone (GH) on this primary lymphoid organ, with emphasis on
data derived from
in vivo experiments. A series of results strongly
indicate that GH enhances thymocyte proliferation in both rodents
and humans. Moreover,
in vivo treatment with GH enhances interleukin
(IL)-6 production by mouse thymocytes, and
ex vivo experiments
show that production of other cytokines, such as IL-1 and GM-CSF,
is also augmented. In a second vein, GH exerts a modulatory
role on thymic hormone production, particularly the secretion
of thymulin. In GH-treated animals as well as GH-transgenic
mice, thymulin secretion is enhanced. In acromegalic patients
we found higher levels of thymulin secretion, whereas the opposite
was seen in dwarf mice and GH receptor knockout animals. Developing
T cell migration is also under GH influence. Recombinant GH
was found to increase human T cell engraftment in the thymus
of SCID mice. Moreover,
ex vivo thymocyte traffic into and out
of thymic nurse cell complexes is enhanced after GH treatment.
Lastly, we show that thymocyte export
in vivo is modulated by
GH, which favors the homing of CD4
+ recent thymic emigrants
towards lymph nodes. In conclusion, the possibility that GH
improves
in vivo thymic functions, including thymocyte proliferation
and migration, points to this molecule as a potential therapeutic
adjuvant in T cell associated immunodeficiencies.
