Author/Authors :
Seyedi، Shahram نويسنده Department of Immunology, Isfahan Medical School, Isfahan University of Medical Sciences, Isfahan, Iran , , Andalib، Alireza نويسنده , , REZAEI، ABBAS ALI نويسنده , , Hosseini، Seyed Mohsen نويسنده Department of Epidemiology and Biostatistics, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran , , Mohebbi، Seyed Reza نويسنده Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran , , Zali، Mohammad-Reza نويسنده , , Vafai، Mohamad نويسنده Iranian Scientific Society of Osteoma Care, Tehran, Iran , , Behboo، Roubik نويسنده Iranian Scientific Society of Osteoma Care, Tehran, Iran , , Tabatabaei، Seyed Abbas نويسنده Department of Thoracic Surgery, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran , , Shahabi، Shahram نويسنده ,
Abstract :
Objective: Anti-tumor immunity and cytokine profiles have important roles in the development
of cancer. Norepinephrine (NE) release due to sympathetic activation leads to
a Th2 deviation via the beta-2 adrenergic receptor Beta-2 adrenergic receptor (B-2AR)
and could increase cancer progression. This study intends to determine the effects of
isoproterenol (ISO; beta-agonist) and propranolol (PRO; beta-antagonist) on the production
of IFN-?, IL-4, and IL-17. Cytokine levels have been examined in tumor-infiltrating
lymphocytes (TILs) and peripheral blood mononuclear cells (PBMCs) of patients
with colorectal cancer (CRC). The B-2AR expression on lymphocyte subsets was also
assessed.
Materials and Methods: In this experimental study, TILs were isolated from fresh CRC
tissue and patient PBMCs were obtained just prior to surgery. The cells were cultured in
medium for 72 hours. Concomitantly, cells were stimulated with 10 ?g/ml phytohemagglutinin
(PHA) alone or in the presence of either 1 ?mol/L of PRO or 1 ?mol/L ISO. The
concentration of cytokines in the supernatants was measured by ELISA. Three-color flow
cytometry was used to determine the expression of B-2AR on the lymphocyte subsets.
Statistical analyses were performed via paired or independent t-test.
Results: Levels of IFN-?, IL-4 and IL-17 were elevated after PHA-stimulation of PBMCs
and TILs. However, the elevation of IFN-? and IL-17 production by TILs in response to PHA
was significantly lower than PBMCs. In the presence of ISO, the IFN-?/IL-4 ratio reduced
in all groups, but this reduction was very low in TILs. Interestingly, the effects of PRO on
cytokine production were, at least partially, comparable to those of ISO. Depressed levels
of B-2AR expression were demonstrated on CD4+IFN-?+ and CD4+IL-17+ lymphocytes
in patients’ PBMCs and TILs.
Conclusion: This study has demonstrated the effects of ISO and PRO on cytokine production
by TILs and determined B-2AR expression on these cells. ISO failed to induce a
shift toward the expected Th2 cytokine profile in CRC patients’ TILs, which might be due to
the downregulation of B-2AR expression on TILs. Additionally, in this study, PRO induced
a shift to a Th2 profile in PBMCs.
