Cellular & Molecular Immunology. 2004 Feb, Vol.1, No.1, pp.63-70.
Type Two Cytokines Predominance of Human Lung Cancer and Its Reverse by Traditional Chinese Medicine TTMP

Haiming Wei¹, Rui Sun^1,2, Wei Xiao³, Jinbo Feng², Chunyan Zhen³, Xiaoqun Xu² and Zhigang Tian^1,2,4
1School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
²Shandong Cancer Biotherapy Center, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, China.
³Shandong University Medical School, Jinan, Shandong 250001, China.
⁴Corresponding Author: School of Life Sciences, University of Science and Technology of China, 443 Huangshan Road, Hefei, Anhui 230027, China. Tel: +86-551-360-7379; Fax: +86-551-360-6783; E-mail: tzg@ustc.edu.cn.

Type 2 cytokines are usually predominant in tumor patients and associated with tumor progression. To explore whether reversing of type 2 predominance could be a promising strategy in tumor immunotherapy, PBMC of 35 lung cancer patients and 19 healthy subjects were prepared and subjected to be examined for cytokine secretion and gene expression. Tetra-Methylpyrazine (TTMP), extracted from a traditional Chinese medicinal herb which has been used in clinic to reverse the Th2 status of cancer patients in China, was added to PBMC culture. Determined by RT-PCR, the positive percentages of mRNA expression of type 1 cytokines (8.6% for IFN-γ and 11.4% for IL-2) were lower than those of type 2 cytokines (71.4% for IL-4, 60% for IL-6 and 80% for IL-10) in patients’ PBMCs. The potential of gene expressing (measured as relative intensity to the ratio of β-actin) in the patients for type 1 cytokines was also in a low level (0.111 for IFN-γ, 0.119 for IL-2) in comparison with a relative high level for type 2 cytokines (0.319 for IL-4, 0.303 for IL-6 and 0.377 for IL-10). Meanwhile, both positive percentage and relative intensity of gene expression were lower for a type 1 cytokine-related transcription factor T-bet (31.4% and 0.142, respectively) than those for type 2 cytokine-related GATA3 (85.7% and 0.378, respectively). The blood serum levels of IFN-γ and IL-2 in the patients were slightly lower but not significantly when compared with healthy control. In contrast, the levels IL-4 and IL-6 in patients were significantly higher than those in healthy subjects by ELISA analysis. TTMP could enhance supernatant concentration and gene expression levels of IFN-γ, IL-2 and T-bet, but reduced those of type 2 cytokines. These results demonstrate that the lung cancer patients had a predominant expression of type 2 cytokines and TTMP could reverse the type 2 dominant status, which might offer an alternative therapeutic regime for lung cancer patients.