Immunological effects of taxol and adryamicin in breast cancer patients

Abstract

Antineoplastic chemotherapy still consists in the major first-line therapeutics against cancer. Several reports have described the immunomodulatory effects of these drugs based on in vitro treatment, but no previous data are known about these effects in patients and its association with immunological-mediated toxicity. In this study, we first characterize the immunological profile of advanced breast cancer patients treated with doxorubicin and paclitaxel protocols, immediately after chemotherapy infusion. Our findings included an immediate plasmatic reduction in IL-1, IL-10, and TNF-α levels in doxorubicin-treated patients, as well as high levels of IL-10 in paclitaxel patients. Further, it was demonstrated that both drugs led to leukocytes oxidative burst impairment. In vitro analysis was performed exposing healthy blood to both chemotherapics in the same concentration and time of exposition of patients, resulting in low IL-10 and high IL-1β in doxorubicin exposition, as low TNF-α and high IL-1 in paclitaxel treatment. Nitric oxide levels were not altered in both in vivo and in vitro treatments. In conclusion, our data revealed for the first time that the immediate effects of chemotherapy could be mediated by cytokines signaling in patients and that the results observed in patients could be a resultant of host immune cells activation.

Fig. 1

Cytokines profile. Pro-inflammatory cytokines TNF-α (a), IL-1β (b) and IL-12 (c), as well the anti-inflammatory IL-10 (d) plasmatic levels were measured as indicators of immunological Th1/Th2 status. Means were evaluated by Student’s unpaired t test. CTR control group, CA patients with breast cancer in TNM stages III and IV, DOX doxorubicin-treated patients 1 h after intravenous infusion of 60 mg/m², PTX paclitaxel-treated patients 1 h after intravenous infusion of 75 mg/m². *indicate statistical difference when r compared to control and ^#when compared to cancer group (P < 0.05)

Fig. 2

Nitric oxide levels and functional evaluation of leukocytes burst. NO levels were evaluated in plasma and leukocytes burst in whole blood. Means were evaluated by Student’s unpaired t test. CTR control group, CA patients with breast cancer in TNM stages III and IV, DOX doxorubicin-treated patients 1 h after intravenous infusion of 60 mg/m², PTX paclitaxel-treated patients 1 h after intravenous infusion of 75 mg/m². *indicate statistical difference when r compared to control and ^#when compared to cancer group (P < 0.05)

Fig. 3

In vitro analysis of cytokines release in whole blood. Pro-inflammatory cytokines TNF-α (a), IL-1β (b) and IL-12 (c), as well the anti-inflammatory IL-10 (d) plasmatic levels were measured as indicators of immunological Th1/Th2 status. Means were evaluated by Student’s unpaired t test. CTR control blood, DOX doxorubicin-treated blood 1 h after treatment with a dose equivalent to 60 mg/m², PTX paclitaxel-treated blood 1 h after treatment with a dose equivalent to 75 mg/m². * indicate statistical difference when r compared to control (P < 0.05)