Evaluation of anti-tumor property of specific and non-specific BRMs in experimental gioma by assessing the microglial cell functional and phenotypic modulations.
BACKGROUND
Microglial cells are considered to be the chief immunomodulatory cells of the brain. These cells play a crucial role against various neurodegenerative diseases. When modulated microglia have been shown to exert a potential anti-tumor immune response against brain neoplasms. Although several specific BRMs like IL-2, IFNgamma have been shown to modulate the microglia to get an effective anti-tumor immune response, associated toxicities and detrimental side effects have posed severe limitation in there use particularly for therapeutic purposes.


OBJECTIVE
In the present study, attempts have been made to elicit the modulations of microglia cell function and phenotypic expression following specific (IL-2, IFNgamma and a novel nonspecific BRM (corpuscular antigen) in order to determine their anti-tumor property in experimental glioma model.


METHODS
Brain was experimentally induced in young Druckray rats of both sexes with N-N-ethyl nitroso urea (ENU). These ENU treated animals were administered with both specific and nonspecific BRMs like IL-2, IFNgamma and SRBC either singly or in combination 5 months after ENU administration and after ascertaining its degree of malignancy.


RESULTS
Microglial cells separated from different experimental groups were found to be positive for CD11b, MHC II, CD4 and negative for GFAP.FACS analysis demonstrated that different subtypes of microglial cell populations (CD25+, MHC II+ and CD25+MHC II+) in the brain tissue based on phenotypic expression, which were downregulated in tumor bearing animals, and subsequently restored with increased expression, particularly with SRBC administration. The Scanning Electron Microscopic (SEM) study also depicted modulation of cellular morphology of microglial cell predominantly with SRBC administration. Studies conducted ton evaluate immunological functions at the cellular level showed increased antigen presenting caopacity of microglial cell with SRBC administration, which was significantly greater then IL-2, IFNgamma and combined doses (E2_S). However phagocytic functions of microglial cells were found not to be significantly modulated with BRM treatment.


CONCLUSIONS
The results suggest that the nonspecific BRM SRBC can exert greater modulatory effect on microglila cell function and phenotypic expression than the other BRMs used, and in doing so culminate in a potent anti tumor immune response in experimental glioma with compatible tolerance profile.
D000818:Animals; D000831:Animals, Newborn; D000938:Antigen-Presenting Cells; D001932:Brain Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D004912:Erythrocytes / Q000276:immunology; D005038:Ethylnitrosourea / Q000633:toxicity; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005910:Glioma / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007111:Immunity, Cellular; D007155:Immunologic Factors / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use*; D008297:Male; D017628:Microglia / Q000648:ultrastructure*; D010587:Phagocytosis; D010641:Phenotype; D051381:Rats; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D015996:Survival Rate
D039481:CD11b Antigen; D015704:CD4 Antigens; D005904:Glial Fibrillary Acidic Protein; D000949:Histocompatibility Antigens Class II; D007155:Immunologic Factors; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma; D005038:Ethylnitrosourea