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Interleukin-5 induces tumor suppression by peritoneal exudate cells in mice
Y Nakashima1, S Mita, K Takatsu
1Department of Surgery II, Kumamoto University Medical School, Japan.
Abstract:
The antitumor activity of peritoneal exudate cells (PEC) induced by murine interleukin-5 (mIL-5) was examined using Meth-A sarcoma cells transplanted into the peritoneal cavity of mice. Although in vitro treatment of Meth-A sarcoma cells with mIL-5 did not result in inhibition of their growth, treatment of mice intraperitoneally with mIL-5 (1 microgram/day) from day -5 to +5 (tumor cells were inoculated on day 0) led to a significant increase in survival or even rejection of tumor cells. This antitumor effect depended on the dose of mIL-5. Interestingly, there was identical therapeutic activity when the protocol of days -10 to -1 was used as opposed to -5 to +5. In addition, post-treatment with mIL-5 from day +1 to +10 was ineffective. This suggests that the therapeutic activity of IL-5 is largely prophylactic. Under the former condition, the number of PEC was found to increase over 50-fold when compared to levels in control mice. Moreover, the antitumor effect of mIL-5 was completely abolished by subcutaneous injection of anti-mIL-5 monoclonal antibodies. The treatment of mice injected intraperitoneally with human IL-2 also resulted in an increase in survival. Winn assay experiments using PEC recovered from mIL-5-treated mice (1 microgram/day, from day -10 to -1) revealed that these PEC could mediate antitumor activity against Meth-A sarcoma cells. Furthermore, when the cured mice were re-injected with Meth-A sarcoma cells or syngeneic MOPC104E cells, they could reject Meth-A sarcoma cells but not MOPC104E cells, indicating that immune memory had been generated. These results suggest that IL-5 augmented the PEC tumoricidal activity but we have no indication that the tumoricidal activity was mediated through a mIL-5-dependent mechanism.
Insights
Murine interleukin-5 (mIL-5) enhances peritoneal exudate cell (PEC) antitumor activity against Meth-A sarcoma in mice. Prophylactic mIL-5 treatment boosts survival and generates immune memory, suggesting IL-5 primes cells for tumor rejection.
Area of Science:
- Immunology
- Cancer Research
- Cell Biology
Background:
- Peritoneal exudate cells (PECs) play a role in antitumor immunity.
- Interleukin-5 (IL-5) is a cytokine involved in immune responses.
- The therapeutic potential of IL-5 against solid tumors requires further investigation.
Purpose of the Study:
- To investigate the antitumor activity of PECs induced by murine interleukin-5 (mIL-5).
- To determine the efficacy of mIL-5 in a murine sarcoma model.
- To explore the prophylactic and therapeutic potential of mIL-5.
Main Methods:
- Meth-A sarcoma cells were transplanted into mice.
- Mice were treated intraperitoneally with mIL-5 at varying doses and schedules.
- Antitumor activity was assessed by survival rates, Winn assays, and immune memory generation.
- Monoclonal antibodies against mIL-5 were used to block IL-5 activity.
Main Results:
- Intraperitoneal mIL-5 treatment significantly increased survival and led to tumor rejection in a dose-dependent manner.
- Prophylactic mIL-5 administration (days -10 to -1 or -5 to +5) was effective, while post-treatment (days +1 to +10) was not.
- mIL-5 treatment increased PEC numbers over 50-fold and induced tumor-specific immune memory.
- The antitumor effect was abolished by anti-mIL-5 antibodies, confirming IL-5's role.
Conclusions:
- Murine interleukin-5 demonstrates significant prophylactic antitumor activity against Meth-A sarcoma in mice.
- IL-5 augments PEC tumoricidal activity, likely through a prophylactic mechanism that primes the immune system.
- The study suggests IL-5's potential as an immunotherapeutic agent for cancer, particularly when administered prior to tumor challenge.