Prolonged Humid Heat Triggers Systemic Inflammation and Stress Signaling: Fluid Intake Modulates NF-κB, p38, JNK2, and STAT3α Pathways
Abstract
1. Introduction
2. Results
2.1. Hydration Status
2.2. Body Temperatures
2.3. Systemic Inflammation and Organ Function
2.4. Oxidative Stress, Intestinal Cell Injury, and Cortisol Levels
2.5. Inflammatory Signaling Pathways
3. Discussion
3.1. Limitations
3.2. Physiological Relevance and Practical Significance
4. Materials and Methods
4.1. Ethical Approval and Participants
4.2. Experimental Protocol
4.3. Measurements
4.3.1. Blood Preparation
4.3.2. Inflammatory Cytokines
4.3.3. Oxidative Stress, Intestinal Cell Injury, and Cortisol
4.3.4. Organ Function Markers
4.3.5. Whole Blood Cell Counts
4.4. Western Blotting
4.5. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
LFI | Limited fluid intake |
FFI | Full fluid intake |
NF-κB | Nuclear factor kappa B |
MAPKs | Mitogen-activated protein kinases |
JAK/STAT | Janus kinase/signal transducer and activator of transcription |
JNK | C-June N-terminal kinase |
IL-6 | Interleukin-6 |
IL-1β | Interleukin-1β |
USG | Urine specific gravity |
Tcore | Core temperature |
Tsk | Mean skin temperature |
IFN-γ | Interferon-γ |
TNF-α | Tumor necrosis factor-α |
ALT | Alanine aminotransferase |
BUN | Blood urea nitrogen |
MDA | Malondialdehyde |
SOD | Superoxide dismutase |
iFABP | Intestinal fatty acid-binding protein |
p-NF-κB p65 | Phosphorylated NF-κB p65 |
p-JNK1 | Phosphorylated JNK1 |
p-JNK2 | Phosphorylated JNK2 |
p-p38 | Phosphorylated p38 |
p-STAT3α | Phosphorylated STAT3α |
p-STAT3β | Phosphorylated STAT3β |
LPS | Lipopolysaccharide |
TLR4 | Toll-like receptor 4 |
HPA | Hypothalamic–pituitary–adrenal axis |
PBMCs | Peripheral blood mononuclear cells |
SIRS | Systemic inflammatory response syndrome |
BP | Blood pressure |
DBP | Diastolic blood pressure |
SBP | Systolic blood pressure |
BCA | Bicinchoninic acid |
PVDF | Polyvinylidene fluoride |
ANOVA | Analysis of variance |
SD | Standard deviation |
CV | Coefficient of variation |
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LFI (Limited Fluid Intake) | FFI (Full Fluid Intake) | |||||||
---|---|---|---|---|---|---|---|---|
Males | Females | Males | Females | |||||
Body temperatures | Pre | Post | Pre | Post | Pre | Post | Pre | Post |
Tcore (°C) | 36.9 ± 0.2 | 38.1 ± 0.3 * | 37.0 ± 0.1 | 38.0 ± 0.3 * | 36.9 ± 0.2 | 37.9 ± 0.4 *# | 37.1 ± 0.1 † | 37.6 ± 0.2 *#† |
Tsk (°C) | 33.8 ± 0.3 | 37.6 ± 0.4 * | 33.0 ± 0.6 | 37.7 ± 0.4 * | 33.9 ± 0.4 | 37.5 ± 0.5 * | 33.5 ± 0.8 † | 37.4 ± 0.2 * |
Cardiovascular | Pre | Post | Pre | Post | Pre | Post | Pre | Post |
SBP (mmHg) | 118 ± 7 | 112 ± 8 * | 113 ± 10 | 105 ± 8 * | 119 ± 9 | 111 ± 7 * | 112 ± 5 † | 103 ± 5 *† |
DBP (mmHg) | 72 ± 6 | 63 ± 7 * | 68 ± 8 | 58 ± 4 * | 70 ± 5 | 63 ± 5 * | 65 ± 5 † | 57 ± 5 *† |
MAP (mmHg) | 87 ± 6 | 79 ± 6 * | 83 ± 7 | 74 ± 4 * | 86 ± 6 | 79 ± 6 * | 81 ± 4 † | 73 ± 5 *† |
HR (bpm) | 65 ± 8 | 118 ± 8 * | 64 ± 7 | 112 ± 13 * | 59 ± 5 | 110 ± 9 * | 63 ± 4 | 113 ± 12 * |
Blood biomarkers | Pre | Post | Pre | Post | Pre | Post | Pre | Post |
Hematocrit (%) | 43.4 ± 3.3 | 46.9 ± 2.0 * | 30.8 ± 3.6 | 37.0 ± 3.7 * | 43.9 ± 3.8 | 46.4 ± 2.0 * | 34.1 ± 2.2 † | 37.0 ± 3.3 *† |
Leukocytes (109/L) | 6.8 ± 1.2 | 13.6 ± 2.0 * | 5.5 ± 0.7 | 10.8 ± 2.4 * | 6.3 ± 1.2 | 12.5 ± 2.0 * | 6.5 ± 0.7 | 10.2 ± 2.0 *† |
Neutrophils (109/L) | 3.5 ± 0.7 | 8.7 ± 1.8 * | 3.1 ± 0.6 | 6.6 ± 0.8 * | 3.3 ± 0.7 | 8.1 ± 1.6 * | 2.9 ± 0.6 | 5.7 ± 1.2 *† |
K+ (mmol/L) | 3.9 ± 0.1 | 4.0 ± 0.2 * | 4.0 ± 0.2 | 4.1 ± 0.3 * | 4.0 ± 0.2 | 3.8 ± 0.3 * | 4.0 ± 0.2 | 3.8 ± 0.5 * |
Na+ (mmol/L) | 144.7 ± 3.4 | 146.1 ± 1.9 * | 142.2 ± 5.3 | 142.7 ± 3.5 * | 142.4 ± 3.0 | 141.1 ± 2.8 * | 142.2 ± 5.3 | 130.0 ± 13.8 *† |
Cl− (mmol/L) | 103.6 ± 3.6 | 110.1 ± 6.2 * | 104.9 ± 2.2 | 105.4 ± 1.5 * | 101.5 ± 3.9 | 99.5 ± 2.3 * | 103.3 ± 4.6 | 97.1 ± 9.6 *† |
PV change (%) | - | −6.7% | - | −7.4% | - | 6.4% | - | 8.7% |
Hydration | Pre | Post | Pre | Post | Pre | Post | Pre | Post |
USG (g/mL) | 1.013 ± 0.005 | 1.030 ± 0.004 * | 1.012 ± 0.003 | 1.030 ± 0.002 * | 1.016 ± 0.007 | 1.014 ± 0.010 *# | 1.011 ± 0.001 | 1.013 ± 0.003 * |
Dehydration rate (%) | - | 3.0 ± 0.5 * | - | 2.8 ± 0.4 * | - | - | - | - |
Sweat rate (g/h) | - | 237 ± 48 * | - | 165 ± 58 * | - | 276 ± 80 * | - | 214 ± 47 *† |
Perceptions | Pre | Post | Pre | Post | Pre | Post | Pre | Post |
Thermal sensation | 0.8 ± 0.5 | 2.6 ± 0.4 * | 0.7 ± 0.5 | 3.3 ± 0.5 * | 0.8 ± 0.5 | 2.5 ± 0.8 * | 0.7 ± 0.5 | 2.7 ± 0.5 *† |
Thermal comfort | −0.5 ± 0.6 | −2.5 ± 0.5 * | 0.5 ± 0.8 | −3.2 ± 0.9 * | −0.7 ± 0.6 | −2.0 ± 0.7 * | 0.3 ± 0.5 † | −2.7 ± 0.5 *† |
Wetness perception | −0.8 ± 0.6 | −2.4 ± 0.5 * | −0.3 ± 0.5 | −3.3 ± 0.5 * | −0.9 ± 0.6 | −2.2 ± 0.5 * | −0.5 ± 0.5 † | −2.7 ± 0.5 *† |
Thirst sensation | 2.1 ± 0.7 | 5.1 ± 0.8 * | 1.2 ± 0.4 | 4.8 ± 0.8 * | 1.6 ± 0.7 | 2.5 ± 1.0 * | 1.8 ± 0.7 | 2.2 ± 0.4 * |
Psychological stress | 0.8 ± 0.7 | 6.5 ± 1.4 * | 1.1 ± 1.0 | 6.3 ± 1.6 * | 0.8 ± 0.8 | 5.0 ± 1.3 * | 0.8 ± 0.9 | 5.5 ± 1.3 * |
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Wang, F.; Lu, C.; Lei, Y.; Lei, T.-H. Prolonged Humid Heat Triggers Systemic Inflammation and Stress Signaling: Fluid Intake Modulates NF-κB, p38, JNK2, and STAT3α Pathways. Int. J. Mol. Sci. 2025, 26, 5114. https://doi.org/10.3390/ijms26115114
Wang F, Lu C, Lei Y, Lei T-H. Prolonged Humid Heat Triggers Systemic Inflammation and Stress Signaling: Fluid Intake Modulates NF-κB, p38, JNK2, and STAT3α Pathways. International Journal of Molecular Sciences. 2025; 26(11):5114. https://doi.org/10.3390/ijms26115114
Chicago/Turabian StyleWang, Faming, Caiping Lu, Ying Lei, and Tze-Huan Lei. 2025. "Prolonged Humid Heat Triggers Systemic Inflammation and Stress Signaling: Fluid Intake Modulates NF-κB, p38, JNK2, and STAT3α Pathways" International Journal of Molecular Sciences 26, no. 11: 5114. https://doi.org/10.3390/ijms26115114
APA StyleWang, F., Lu, C., Lei, Y., & Lei, T.-H. (2025). Prolonged Humid Heat Triggers Systemic Inflammation and Stress Signaling: Fluid Intake Modulates NF-κB, p38, JNK2, and STAT3α Pathways. International Journal of Molecular Sciences, 26(11), 5114. https://doi.org/10.3390/ijms26115114