INTRODUCTION
Oxygen Species change the frequency of T lymphocyte subsets and reduce the antioxidant levels in humans or animals (3). Interleukin beta1 (IL-1β) and Tumor necrosis factor alpha (TNF-α) are key proinflammatory cytokines the levels of which increase in response to inflammation. Both of them are involved in a variety of cellular activities (cell proliferation, differentiation, and cell death). However, they have different structures, cellular responses, and activation pathways (5). C-reactive protein (CRP), the level of which is mainly regulated by the action of some cytokines, especially interleukin-6, is one of the practical methods reducing inflammatory factors in regular exercise, which acts as a natural antioxidant and a safe anti-inflammatory strategy to prevent and control the complications of diseases (7). Studies have shown that high-intensity and resistance physical activity suppresses the expression of IL-1β, TNF-α, and CRP genes, which are pro-inflammatory and inflammatory factors (8, 9). Some previous studies have shown that pollen (pollen of all spring flowers) due to its phenolic compounds, phenolic acids, flavonoids, and significant amounts of minerals and vitamins (e.g., vitamin C) has a wide range of biological functions, including antioxidant, anti-inflammatory, antimicrobial, anti-allergic, anti-tumor, and anti-atherosclerotic properties, which have favorable effects on the functions of the nervous, immune, and inflammatory systems (11,12). It also strengthens the antioxidant system (13,14). In this context, Takahashi et al. reported that bee pollen supplementation can inhibit the production of proinflammatory cytokines, TNF-α, IL-6, and CRP by stimulating macrophages and interferon-gamma (15).

METHODS
In this experimental study, 25 healthy male Sprague-Dawley rats, approximately eight weeks old and weighing approximately 250 grams, were obtained from the Center for Animal Breeding and Reproduction of Islamic Azad University, Marvdasht Branch, Iran, and were transferred to the animal exercise physiology laboratory at a temperature of 22±2 °C, a humidity of 50%-55%, and a 12:12 hour light-dark cycle until the end of the experiments and exercise training period. After one week of adaptation to the laboratory environment and familiarization with the treadmill, the rats were matched based on weight and randomly divided into 5 equal groups (n=5), including control, cadmium, cadmium-pollen, cadmium-high-intensity interval training, and cadmium + pollen + high-intensity interval training. A high-intensity interval training program was performed for 8 weeks, which included three weekly sessions of running on a rodent treadmill at an intensity of 80% to 110% VO2 max. The mice were treated with pollen by oral gavage daily. All groups, except for the healthy control group consumed cadmium chloride (40 mg/kg/w/d dissolved in drinking water). Then, 48 hours after the last training session, pollen supplementation, and water-soluble cadmium chloride consumption, the mice were anesthetized using ketamine (50 mg/kg) and xylazine (20 mg/kg) in a 12-hour fast. To confirm cadmium poisoning and measure inflammatory factors, after complete anesthesia and dissection, the hippocampal tissue of the brain was carefully extracted and stored at -70°C until data collection and analysis. Two-way analysis of variance and t-test were used to analyze the data at a significance level of P<0.05.

RESULTS
The results of the independent t-test showed that the levels of cadmium in the brain were significantly lower in the healthy control group than in the other groups (P=0.001). These results also showed a significant decrease in the rate of change in cadmium levels in the exercise-pollen group, compared to the cadmium group (P=0.031). However, these levels were not significant, compared to the pollen (P=0.204) and the exercise groups (P=0.278). The same test for IL-1β levels showed that they were significantly lower in the healthy control group, compared to the cadmium (P=0.005), pollen (P=0.032), and exercise groups (P=0.003). However, the exercise-pollen group showed no significant difference (P=0.425). After 8 weeks of training and pollen consumption, IL-1β values in the pollen (P=0.898), the exercise (P=0.880), and the exercise + pollen groups (P=0.056) did not show a significant decrease, compared to the cadmium group. TNF-α values in an independent t-test showed that they were significantly lower in the healthy control group than in the cadmium (P=0.016), pollen (P=0.002), and exercise groups (P=0.012). However, this difference was not significant for the exercise + pollen group (P=0.245). After 8 weeks of training and pollen consumption, TNF-α values in the pollen (P=0.365), exercise (P=0.258), and exercise + pollen groups (P=0.132) did not show a statistically significant decrease, compared to the cadmium group. Also, the healthy control group showed a significant difference in terms of CRP values, compared to the cadmium (P=0.001), pollen (P=0.045), and exercise groups (P=0.003). However, this difference was not significant for the exercise + pollen group (P=0.106). After 8 weeks of exercise and pollen consumption, the CRP values in the pollen (P=0.029) and the exercise-pollen groups (P=0.005) showed a significant difference, compared to the cadmium group. However, this difference was not significant in the exercise group (P=0.267).

CONCLUSION
According to the results of this study, performing intense interval training with pollen consumption did not significantly reduce the levels of IL-1β and TNF-α; moreover, intense interval training alone and with pollen is unable to reduce CRP levels in mice exposed to cadmium. However, pollen consumption alone reduced CRP levels. Therefore, it seems that intense interval training and pollen consumption may not be effective in reducing some inflammatory factors, which in the present study is probably related to the difference in the type of subject, training methods, insufficient repetition, intensity, and duration of training and the use of the type of disease, as well as the high dose of toxic cadmium, and the dose of pollen consumed during the intervention, which has a non-uniform and different response affecting the immune system.
 

Ethical Considerations
Compliance with ethical guidelines
All ethical principles for working with animals were approved in accordance with the Helsinki Declaration and under the supervision of the Ethics Committee of the Islamic Azad University, Boroujerd Branch, Boroujerd, Iran (IR.IAU.B.REC.1402.114).

Funding
No financial support was provided for this research.

Authors' Contributions
All authors participated in the design, implementation, data analysis, and writing of all parts of the study.

Conflict of Interest
The authors of this article declare that they have no conflicts of interest.

Acknowledgments
The authors hereby express their gratitude and appreciation to all those who collaborated in this research.