IL-11 synergizes with IL-3 in promoting the recovery of the immune system after irradiation

In our previous studies aiming at the design of appropriate strategies to accelerate the recovery of the immune system after irradiation, we found that recombinant murine (rmu) IL-3 treatment induces differentiation and growth of thymocytes and splenic T and B lymphocytes in mice exposed to X-rays (200-500 cGy). These studies were extended to investigate the effects of recombinant human (rhu) IL-11. Results indicate that rhulL-11 is able to restore thymus and spleen cell numbers as well as T and B cell mitotic responsiveness in mice exposed to 200 cGy but not to 300 cGy. However, recovery of thymus and spleen cell numbers and functions could be accelerated also in mice exposed to higher doses if rhuIL-11 was given with rmuIL-3. Recovery was complete as soon as 7 days after irradiation. A large dose range of both cytokines was explored and the synergistic effect of the two cytokines was evident when a relatively small dose of rhuIL-11 was injected with graded doses of rmuIL-3, The recovery of the immune system in irradiated mice injected with these cytokines was independent from Bcl-2 expression, suggesting that elimination of damaged cells by apoptosis is unaffected by hematopoietic cytokines.