Paraneoplastic neurodegeneration in a murine host following progressive growth of a spontaneous T-Cell lymphoma: role of proinflammatory internal responses.

Objective(s): In the present study, the mechanism of paraneoplastic neurodegeneration associated with progressive in vivo growth of a T-cell lymphoma of spontaneous origin has been investigated.
Methods: Histologically, the brain was investigated by hematoxylin-eosin staining of brain sections. Western blotting was performed to detect the expression of cytokines and other proteins. Macrophage-derived interleukin-1 (IL-1) and tumor necrosis factor (TNF) was estimated by immunoassays. Induction of apoptosis in brain and tumor cells was determined by percent specific DNA fragmentation.
Results: Tumor growth was associated with the development of multiple lesions in various regions of the brain along with alterations in the structure and alignment of Purkinje cells, and an increase in the water content in the brain. Brain extract and serum of tumor-bearing mice showed higher levels of proinflammatory cytokines. Induction of apoptosis is suggested to be the cause underlying the loss of cellularity of tumor-bearing hosts in the brain owing to an augmentation in the induction of the caspase-dependent pathway of programmed cell death. Further, the study presents investigations to show the role of nitric oxide and proinflammatory cytokines IL-1, TNF, interferon-gamma and alkaline phosphatase in the manifestation of paraneoplastic neurodegeneration.
Conclusions: Growth of a T-cell lymphoma is associated with the manifestation of neurodegeneration caused by soluble proinflammatory factors of tumor and/or host origin.