Immunotherapy with natural interleukins and/or thymosin alpha 1 potently augments T-lymphocyte responses of hydrocortisone-treated aged mice.
Cytokines and thymic hormones are thought to play critical roles in the regulation of T-lymphocyte development and function. In an effort to determine the effectiveness of such agents in an immunotherapeutic strategy, we employed aged mice in a hydrocortisone treatment model to generate an immunodeficient state and to study its reconstitution. Mice were given five daily injections of a natural cytokine mixture (NCM), recombinant interleukins (rIL-1, rIL-2) or their combination, thymosin alpha 1 or fraction 5 (T alpha 1, TF5), or the combinations of NCM plus T alpha 1 and of NCM plus TF5. Spleen and thymus weights were obtained and the cellular responses to stimulation in vitro with NCM, IL-1, IL-2 and mitogens (PHA and Con A) were assayed. Both NCM and T alpha 1 in vivo treatment augmented thymocyte and splenocyte in vitro responses to both interleukins and mitogens. Neither treatments with equivalent doses of rIL-1, rIL-2 nor their combination, nor TF5 achieved similar results. Of all the treatments, only NCM plus T alpha 1 augmented spleen weight; none augmented thymus weight. Surface marker analyses of T-lymphocytes and subsets indicate that treatment of mice with NCM plus T alpha 1 increased spleen T-cell numbers of both CD4 and CD8 positive cells significantly. These data indicate that NCM and T alpha 1 alone and in combination may be therapeutically useful to restore T-lymphocyte number or function in secondary immunodeficiency.
Hadden
J W
JW
Department of Internal Medicine, University of South Florida, Tampa 33612, USA.
Saha
A
A
Sosa
M
M
Hadden
E M
EM
D000367:Age Factors; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006801:Humans; D006854:Hydrocortisone; D016867:Immunocompromised Host / Q000187:drug effects*; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007958:Leukocyte Count / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects*; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013950:Thymus Gland / Q000187:drug effects
D007375:Interleukin-1; D007376:Interleukin-2; D011994:Recombinant Proteins; D013947:Thymosin; D000077596:Thymalfasin; D006854:Hydrocortisone