Longitudinal analysis of T-helper cell phenotypes in renal-transplant recipients undergoing growth hormone therapy.
BACKGROUND
Treatment with recombinant human growth hormone (rhGH) in growth-retarded children after renal transplantation is effective, but there have been concerns regarding the safety of rhGH because of its possible immunomodulatory actions. We therefore evaluated the immune phenotypes of pediatric renal-transplant recipients and controls in response to rhGH with regard to a possible shift toward a T-helper (TH)1-type response.


METHODS
Intracellular cytokines, activation markers, costimulatory, and adhesion molecules were studied in 13 children after renal transplantation (Tx+GH). Children with chronic renal failure (CRF+GH, n=11) before and under rhGH therapy and pediatric renal-transplant recipients without rhGH therapy (Tx, n=33) served as controls. Measurements were performed by four-color flow cytometry before and 4, 12, 18 and 24 weeks after initiation of rhGH therapy.


RESULTS
Under baseline conditions, Tx+GH patients did not differ from Tx patients. During rhGH therapy in children with transplants, interleukin (IL)-2 production increased threefold at 4 weeks, and IL-4 and IL-13 increased by 70% at 12 weeks. All three cytokines returned to baseline after 18 weeks. No patient experienced rejection. In CRF+GH patients, baseline values for all investigated cytokines were higher than in patients with transplants but did not change in response to rhGH therapy.


CONCLUSIONS
Our data indicates that rhGH therapy in stable, pediatric renal-transplant recipients has a mild and transient immunostimulatory effect in vivo. Immunosuppression and graft function in patients with transplants undergoing rhGH treatment should therefore carefully be monitored.
Melk
Anette
A
Department of Transplantation Immunology, University of Heidelberg, Heidelberg, Germany. anette.melk@med.uni-heidelberg.de
Daniel
Volker
V
Mehls
Otto
O
Opelz
Gerhard
G
Tönshoff
Burkhard
B
D000293:Adolescent; D016516:CD4-CD8 Ratio; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000097:blood; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006130:Growth Disorders / Q000150:complications / Q000188:drug therapy*; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000601:surgery*; D016030:Kidney Transplantation; D008137:Longitudinal Studies; D008297:Male; D010641:Phenotype; D011994:Recombinant Proteins / Q000627:therapeutic use*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D016207:Cytokines; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D016572:Cyclosporine