## 3 Results
### Effects of Caffe on Culture Cytokine, MDA and cAMP Concentrations  
Significant effects of caffeine were found for TNF-\(\alpha\) stimulated production (_p_ = 0.014) (Table 2). Caffeine induced lower TNF-\(\alpha\) concentrations, with a significant decrease in comparison to the control only for the highest (50 \(\upmu\)M) caffeine concentration (_p_ = 0.016). Caffeine did not influence IL-10 (_p_ = 0.208), IL-6 (_p_ = 0.543), IL-12 (_p_ = 0.700) nor IL-1\(\beta\) (_p_ = 0.501)--stimulated production. No effects of caffeine were observed for unstimulated cytokine production (Table S1). Furthermore, caffeine did not influence MDA culture concentrations (_p_ = 0.227).  
When the effect of caffeine on the stimulated cytokine production was analyzed in samples stratified by sex, no significant effect was observed (results not shown).  
Figure 1 shows cAMP culture concentrations expressed as the difference between the concentrations in the stimulated and unstimulated samples. A significant effect of caffeine  
\begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Parameter** & **All** & **Men** & **Women** & **\(p\) Value** \\  & **(_n_ = 10)** & **(_n_ = 5)** & **(_n_ = 5)** & **(_n_ = 5)** \\ \hline Age (years) & \(36.5\pm 6.5\) & \(35.8\pm 8.1\) & \(37.2\pm 5.3\) & 0.754 \\ Body mass (kg) & \(68.5\pm 11.6\) & \(70.6\pm 14.6\) & \(66.4\pm 9.0\) & 0.599 \\ Stature (cm) & \(169.7\pm 7.0\) & \(173.6\pm 5.7\) & \(165.8\pm 6.3\) & 0.073 \\ BMI (kg:\(\mathrm{m}^{-2}\)) & \(23.8\pm 3.4\) & \(23.3\pm 3.9\) & \(24.2\pm 3.3\) & 0.722 \\ Leukocytes (\(10^{3}\cdot\mathrm{mL}^{-1}\)) & \(5.28\pm 1.07\) & \(5.34\pm 1.40\) & \(5.22\pm 0.78\) & 0.871 \\ Lymphocytes (\(10^{3}\cdot\mathrm{mL}^{-1}\)) & \(1.53\pm 0.37\) & \(1.65\pm 0.39\) & \(1.41\pm 0.35\) & 0.334 \\ Monocytes (\(10^{3}\cdot\mathrm{mL}^{-1}\)) & \(0.35\pm 0.13\) & \(0.38\pm 0.17\) & \(0.32\pm 0.07\) & 0.495 \\ \hline \hline \end{tabular} Values are expressed as means \(\pm\) SD.  
\end{table}
Table 1: General characteristics of participants in the study.  
\begin{table}
\begin{tabular}{c c c c c c c c} \hline \hline  & & \multicolumn{4}{c}{**Caffeine Concentrations (\(\upmu\)M)**} & & **ANOVA** \\ \hline  & Control & 5 & 10 & 15 & 30 & 50 & \(p\) (\(\mathrm{n}^{2}\)) \\ \hline IL-10 (pg:\(10^{-3}\) cells) & \(21.9\pm 3.4\) & \(22.1\pm 6.5\) & \(20.6\pm 3.9\) & \(22.7\pm 4.5\) & \(24.0\pm 4.9\) & \(24.6\pm 3.9\) & 0.208 (0.137) \\ IL-6 (pg:\(10^{-3}\) cells) & \(385.2\pm 88.6\) & \(448.2\pm 96.3\) & \(451.5\pm 9.98\) & \(412.4\pm 82.5\) & \(440.6\pm 107\) & \(396.1\pm 93.6\) & 0.543 (0.070) \\ TNF-\(\alpha\) (pg:\(10^{-3}\) cells) & \(58.6\pm 10.4\) & \(57.5\pm 9.8\) & \(55.2\pm 9.4\) & \(49.2\pm 9.1\) & \(47.9\pm 8.3\) & \(45.1\pm 7.7\pm 0.014\) (\(\mathrm{m}^{-2}\)) \\ IL-12 (pg:\(10^{-3}\) cells) & \(4.13\pm 0.84\) & \(4.50\pm 0.78\) & \(5.01\pm 0.11\) & \(4.91\pm 0.66\) & \(4.36\pm 0.8\) & \(4.50\pm 0.95\) & 0.700 (0.053) \\ IL-12 (pg:\(10^{-3}\) cells) & \(17.2\pm 5.0\) & \(19.3\pm 6.0\) & \(18.2\pm 5.3\) & \(19.4\pm 4.8\) & \(16.8\pm 6.3\) & \(20.1\pm 5.1\) & 0.501 (0.073) \\ MDA (nM) & \(0.62\pm 0.10\) & \(0.63\pm 0.12\) & \(0.72\pm 0.13\) & \(0.72\pm 0.12\) & \(0.62\pm 0.11\) & \(0.58\pm 0.11\) & 0.227 (0.147) \\ \hline \hline \end{tabular} Values are expressed as means \(\pm\) SD and represents the percentage with respect to the control. *_p_ < 0.05 indicates significant differences (ANOVA one-way test). # Indicates significant differences vs. control. \(\eta^{2}\) value is provided as a measure of effect size.  
\end{table}
Table 2: Effects of caffeine on LPS-stimulated cytokine production and MDA concentration.  
was found for supernatant cultured cAMP concentrations (\(p\) = 0.001, \(\eta^{2}\) = 0.354). However, only the highest caffeine concentration had a significantly higher cAMP concentration in comparison with the control (\(p\) = 0.006). For the remaining concentrations, no significant differences were observed, with \(p\)-values ranging from 0.052 to 1.000.