Restoration of immune system function is accelerated in immunocompromised mice by the B-cell-tropic isoxazole R-11.
BACKGROUND
Restoration of impaired immune response in immunocompromised patients is a crucial problem. In this study we evaluated the efficacy of isoxazole R-11 in reconstitution of the immune response in immunosuppressed mice.


METHODS
Mice were given a sublethal dose (250 mg/kg b.w.) of cyclophosphamide (CP). The cellular immune response to ovalbumin (OVA) and the humoral immune response to sheep erythrocytes (SRBC) were generated. R-11 was administered at repetitive, intraperitoneal doses (20 μg/mouse) until determination of the immune responses: 7 and 15 doses on alternate days for cellular and humoral immune response, respectively. For phenotypic studies R-11 was given per os, at a single dose of 20 μg/mouse. The ability of R-11 to affect interleukin- 6 (IL-6) production was determined in the whole human blood cell culture.


RESULTS
R-11 increased the content of CD19+ cells in the spleens and lymph nodes with a concomitant decrease of CD3+ and CD4+ cells. The compound significantly accelerated restoration of both cellular and humoral immune responses, elevated the numbers of circulating leukocytes and splenocytes and normalized the blood cell picture. Supplementary experiments showed that R-11 was not toxic with regard to human peripheral blood mononuclear cells (PBMC) and that it upregulated IL-6 production in blood cell culture stimulated with lipopolysaccharide (LPS).


CONCLUSIONS
We demonstrated that R-11 is likely a B-cell tropic agent which can restore both cellular and humoral immune responses in immunocompromised mice and may have a potential to be applied in therapy of immunocompromised patients.
Laboratory of Immunobiology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, PL 53-114 Wrocław, Poland. zimecki@iitd.pan.wroc.pl
Michał
M
Zimecki
Jolanta
J
Artym
Maja
M
Kocięba
Bożena
B
Obmińska-Mrukowicz
Marcin
M
Mączyński
Stanisław
S
Ryng
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D000284:Administration, Oral; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D003520:Cyclophosphamide / Q000009:adverse effects; D004334:Drug Administration Schedule; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D056724:Immunity, Humoral / Q000187:drug effects*; D016867:Immunocompromised Host / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007555:Isoxazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D015394:Molecular Structure; D010047:Ovalbumin / Q000276:immunology; D012756:Sheep / Q000097:blood; D013154:Spleen / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D007555:Isoxazoles; D008070:Lipopolysaccharides; C440499:lipopolysaccharide, Escherichia coli O111 B4; D003520:Cyclophosphamide; D010047:Ovalbumin