Effects of infliximab, an anti-TNF-α, on cyclophosphamide-induced bone marrow toxicity

Cyclophosphamide is a widely used anticancer agent, though its clinical application is often constrained by myelotoxicity. Infliximab, a monoclonal antibody targeting TNF-α, may alleviate this toxicity by mitigating oxidative stress. This study aimed to assess the protective effects of infliximab against cyclophosphamide-induced myelotoxicity, focusing on bone marrow and spleen-related parameters.

Male Wistar rats (260 ± 20 g) were randomly divided into four groups (n = 5 each): Control (normal saline), Infliximab (7 mg/kg, IP), Cyclophosphamide (200 mg/kg, IP), and Infliximab + Cyclophosphamide (same respective doses with a four-day interval between administrations). Nine days after the initiation of the experiment, bone marrow and spleen histopathology, bone marrow cellularity, spleen index, and levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in bone marrow tissue, along with serum TNF-α and G-CSF concentrations, were evaluated.

Infliximab prevented myelofibrosis in bone marrow tissue; however, it did not mitigate cellularity depletion. It failed to counteract the effects of cyclophosphamide on spleen histology and the spleen index. Additionally, infliximab enhanced antioxidant activity in the bone marrow. Moreover, inhibition of TNF-α was associated with an increase in G-CSF levels.

Although infliximab improved molecular pathways associated with cyclophosphamide-induced bone marrow and hematologic toxicity in the rat model, it did not lead to significant improvements in clinical manifestations.