Impaired production of Th1 cytokines and increased frequency of Th2 subsets in PBMC from advanced cancer patients

Abstract

Background: A reported imbalance of Th1 and Th2 may be responsible for the occurrence and progress of certain diseases. Patients with advanced cancer may have impaired cell-mediated immunity caused by a switch from Th1 to Th2. We investigated the balance of Th1 and Th2 in cancer patients using two approaches.

Methods: Flow cytometry was used to define Th1 and Th2 using intracellular cytokines, thereby determining the frequency of these helper T cells in CD4+ peripheral blood mononuclear cells (PBMC). The amount of cytokines secreted by stimulated PBMC in bulk culture was determined.

Results: Production of TNF-alpha and IFN-gamma in the culture was significantly lower in 9 patients (1188 +/- 634 pg/ml and 46 +/- 84 pg/ml) than in 10 healthy subjects (2491 +/- 1037 pg/ml and 295 +/- 219 pg/ml) (p < 0.002 and p < 0.003), while the production of IL-4 was slightly higher in cancer patients than in the healthy subjects. The percentage of IFN-gamma-IL-4+ cells in CD4+ cells was significantly higher in the patients than in healthy subjects (4.3 +/- 2.0% and 2.4 +/- 0.7%); there was no difference in IFN-gamma+IL-4- cells between the two groups. The ratio of IFN-gamma+IL-4- and IFN-gamma-IL-4+ cells per individual was significantly lower in the patients.

Conclusion: These results indicated that an imbalance of Th1 and Th2 was found not only in the frequency of the subsets in PBMC, but also in the capacity for cytokine-production.