Immunopharmacology of Thymosin ?1 and Cytokine Synergy
Thymosin ?1 (T?1) is a 28 amino acid biologically active protein cleaved from positions 229 of a precursor protein, prothymosin ?. Since its discovery, T?1 has been administered to animals and humans in a wide variety of settings and its pharmacologic effects are to enhance cellular immunity. T?1 administration is highly effective in settings where irradiation, chemotherapy, tumor burden, or immune senescence have caused a reduction of T cell number and/or function. Recent in vitro studies, including the one reported here, suggest that T?1 may act via pathways commonly used by various cytokines. This raises the possibility that T?1 and cytokines may have synergistic activity through potentiation of cytokine activity by T?1. Improved control of tumor growth when tumor-bearing mice were treated with T?1 and high doses of IL-2 has been previously reported. We extended those studies with the Lewis lung carcinoma mouse model using IRX-2, a natural well-defined biologic containing multiple cytokines, in combination with T?1 (IRX-3). Although IRX-2 was effective alone (using doses that contain significantly less IL-2 than in most typical studies), adding T?1 led to significant improvement in survival of the tumor-bearing mice. Based on these observations, the immunopharmacology of T?1 predicts an important clinical role for T?1 in the restoration of cellular immune activity when used in combination with cytokines. Patients who experience immune suppression due to the presence of tumor, irradiation, and/or chemotherapy or aging of the host would most benefit from this treatment combination
thymosin ?1 irx-2 thymus t lymphocytes