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Effect of cyclophosphamide on the immune response to Pseudomonas aeruginosa in mice
Abstract:
Natural resistance in mice to Pseudomonas aeruginosa was decreased 10-fold with a single dose of 300 mg of cyclophosphamide (CY) per kg intraperitoneally. Mice were resistant to infection when immunized actively with Pseudomonas vaccine or passively with Pseudomonas immune serum before receiving CY. Syngeneic spleen, thymus and/or bone marrow cells were transfused into CY-treated recipient mice. Protective anti-Pseudomonas antibody was elicited in the recipient mice when they were vaccinated 1 day after receiving normal spleen cells and challenged 8 days after vaccination. When 1.6 X 10(7) normal thymus and bone marrow cells were infused before vaccination, 69% of the recipients of both cell preparations responded serologically compared with 15 and 27% of those receiving either thymus or bone marrow cells, respectively. CY-treated thymus or bone marrow cell recipients were resistant to Pseudomonas infection when 6 X 10(7) of either cell population was transfused.
Insights
Cyclophosphamide (CY) treatment severely weakened mice's natural defense against Pseudomonas aeruginosa. However, transfusing spleen, thymus, or bone marrow cells, especially combined, restored resistance and antibody production in CY-treated mice.
Area of Science:
- Immunology
- Microbiology
- Pharmacology
Background:
- Natural resistance to Pseudomonas aeruginosa infection in mice can be significantly compromised.
- Cyclophosphamide (CY), an immunosuppressive agent, reduces this natural resistance by a factor of 10.
- Understanding the mechanisms of immune reconstitution is crucial for managing infections in immunosuppressed individuals.
Purpose of the Study:
- To investigate the efficacy of syngeneic cell transfusions in restoring resistance to Pseudomonas aeruginosa in cyclophosphamide-treated mice.
- To determine the role of spleen, thymus, and bone marrow cells in reconstituting immune function and antibody production post-CY treatment.
- To evaluate the combined effect of thymus and bone marrow cell infusions on serological response and infection resistance.
Main Methods:
- Mice were treated with cyclophosphamide (300 mg/kg) to induce immunosuppression.
- Immunization with Pseudomonas vaccine or passive immunization with immune serum was performed before CY administration.
- Syngeneic spleen, thymus, and/or bone marrow cells were transfused into CY-treated mice.
- Vaccination and challenge protocols were employed to assess serological response and resistance to Pseudomonas aeruginosa infection.
Main Results:
- Cyclophosphamide treatment markedly decreased natural resistance to Pseudomonas aeruginosa.
- Pre-immunization with vaccine or immune serum conferred resistance to CY-treated mice.
- Transfusion of syngeneic spleen, thymus, or bone marrow cells into CY-treated mice led to the elicitation of protective anti-Pseudomonas antibody.
- Combined infusion of thymus and bone marrow cells (1.6 X 10^7) resulted in a 69% serological response rate, significantly higher than individual cell types.
- High cell doses (6 X 10^7) of thymus or bone marrow cells conferred resistance to Pseudomonas infection in CY-treated recipients.
Conclusions:
- Cyclophosphamide significantly impairs natural immunity against Pseudomonas aeruginosa.
- Syngeneic hematopoietic cell transplantation, particularly involving thymus and bone marrow, can restore immune competence and protective antibody production in immunosuppressed mice.
- Cellular immunotherapy strategies involving thymus and bone marrow cells show promise for enhancing resistance to bacterial infections in immunocompromised hosts.