Type two cytokines predominance of human lung cancer and its reverse by traditional Chinese medicine TTMP.
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-gamma 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 beta-actin) in the patients for type 1 cytokines was also in a low level (0.111 for IFN-gamma, 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-gamma 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-gamma, IL-2 and T-bet, but reduce 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.
Wei
Haiming
H
School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
Sun
Rui
R
Xiao
Wei
W
Feng
Jinbo
J
Zhen
Chunyan
C
Xu
Xiaoqun
X
Tian
Zhigang
Z
D000328:Adult; D000368:Aged; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D016207:Cytokines / Q000145:classification / Q000235:genetics / Q000276:immunology*; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005260:Female; D015870:Gene Expression; D006801:Humans; D030004:Ligusticum; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D008875:Middle Aged; D011719:Pyrazines / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D011719:Pyrazines; C017953:tetramethylpyrazine