Additive effects of infection and neutropenia on the induction of granulocytopoietic activity in vivo

BACKGROUND. Granulocyte-colony stimulating factor (G-CSF) is a potent stimu lator of granulocytopoiesis and granulocyte function. II has been used in t he treatment of children with neutropenic infection; in this context, it wa s expected to shorten aplasia and limit the severity of infection. Clinical trials, however, have demonstrated conflicting results as to whether these aims can be met. Recently, the use of other, less lineage specific growth factors, such as interleukin (IL)-11 and stem cell factor (SCF), has also b een discussed. The dynamics of growth factors and growth factor-regulating proteins during neutropenic infection, particularily in youngsters, are not well understood. METHODS. Serial blood samples from children and adolescents with infection during chemotherapy-induced neutropenia were assayed for C-reactive protein , white blood cell count, IL-11, SCF, C-CSF, IL-10, IL-4, IL-1 alpha, and I L-1 beta. RESULTS. Although no correlation could be demonstrated between endogenous I L-11 or SCF levels, infection, and leukocyte counts, endogenous G-CSF level s were increased during both aplasia and infection. However, only the addit ive effects of infection and neutropenia led to maximally stimulated endoge nous G-CSF levels. CONCLUSIONS. The elevated G-CSF levels in a majority of patients during sev ere neutropenic infection may explain why a therapeutic benefit of G-CSF tr eatment cannot be demonstrated in all cases;There remains, however, a subgr oup of patients in whom infection and cytopenia do not yield a good G-CSF r esponse. This latter group should be identified, because they might derive some benefit from adjuvant growth factor therapy. The authors predict that the efficacy of G-CSF in the treatment of patients with neutropenic fever m ight depend on each individual's ability to initiate the necessary cytokine production. Cancer 1999;86: 340-8. (C) 1999 American Cancer Society.