A hot day might not seem like a threat that the immune system would need to deal with. But as climate change brings higher average temperatures and more frequent deadly heat waves, the body’s sprawling defense network will start to feel the heat. That sweltering weather could potentially impact the immune system’s ability to fend off microbial marauders and keep the body healthy.
A team of scientists recently untangled how short-term heat exposure affects the body’s defense network in a study presented at a conference in Chicago that was held by the American Heart Association in March. The researchers took one-time blood samples from 624 individuals in Louisville, Ky., as temperatures fluctuated in the summers of 2018 and 2019, and they analyzed various immune molecules that served as biomarkers for inflammation and an immune response. The average temperature when the blood draws occurred was a balmy 75 degrees Fahrenheit (24 degrees Celsius), with most temperatures falling between 69 and 80 degrees F (21 and 27 degrees C), yet the researchers found a sweep of inflammatory changes among study participants on the days that were warmer than average, suggesting that even mild heat was causing the immune system to go into fight mode and expend valuable resources. These findings have researchers considering long-term consequences of rapidly rising global temperatures on immune function.
The new research found that higher temperatures seemed to rouse the immune system’s first responders that normally awaken to a microbial breach. Among those sentinels were signaling proteins called cytokines and multiple types of white blood cells, namely the “first-pass weeders” known as natural killer T cells and the cleanup crew comprised of cells called monocytes. Elevated levels of these cells are signs of inflammation, which is one way the immune system protects against invaders. If prolonged, this aggravation can be harmful to the body.
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The study team also observed differences in the body’s adaptive immunity response, which is generated by cells that act like special operations forces to target specific invaders. Participants whose blood draw occurred when temperatures were high had lower numbers of B cells, the antibody-producing workhorses that recognize specific pathogens and remember them for future infections.
The immune changes were striking, given that Louisville didn’t experience any major warm spells during the study period. “I didn’t expect to see so many cells changing, so many markers changing, especially with this moderate temperature increase,” says Daniel W. Riggs, the study’s first author and a professor of medicine at the University of Louisville.
The city has since undergone scorching heat waves in the fall of 2019 and last summer. Riggs expects that the immune swings are larger when people experience more extreme temperatures.
Other experts say it’s still too soon to say whether the fluctuations in biomolecules are benign or dangerous. “We don’t want to overinterpret” the observed changes, says Sharon Evans, a professor of oncology at Roswell Park Comprehensive Cancer Center, who wasn’t involved in the research. The study, which Evans calls “really exciting,” clearly suggests that “something’s happening” in the immune system.
Riggs’s team thinks the observed signs of inflammation during higher temperatures may erode a person’s health if triggered often. Monocytes contribute to atherosclerosis, a buildup of plaque inside blood vessel walls. Over time, that buildup can lead to a heart attack or stroke.
The effects of heat on the body’s ability to ward off pathogens, however, is less clear. The study researchers say that if there are fewer B cells prowling the bloodstream, the body could be more susceptible to infections. A lower B cell count in the blood, Evans says, could mean that the tiny troopers have instead congregated elsewhere, potentially in defensive positions in the spleen or lymph nodes, where antigens—or molecules from pathogens—first collect. Although a blood sample may indicate fewer B cells in this scenario, the body is better prepared to grapple with pathogens.
Some heat can occasionally be helpful, Evans says. She and other researchers have shown in previous experiments on mice and in cell cultures that short-term moderate heat exposure can in fact shore up immune defenses, such as by enhancing the mobility of white blood cells and blood concentration of immune-signaling molecules. Researchers think the body kicks up a fever to give the immune system a fighting edge during an infection.
Of course, too much heat for long periods, be it from fevers or the environment, can be detrimental. Prolonged fevers strain internal organs such as the heart and lungs, can cause seizures and are metabolically costly. Chronic heat exposure from the environment causes a myriad of known health issues, but Evans predicts that it can also eventually shut down immunity when energy resources are shunted toward cooling the body rather than defending it. A 2019 study showed that mice housed in 97-degree-F enclosures for more than a week had an impaired immune response when they were infected with the influenza virus. This heat exposure is extreme, however, and not representative of real-world conditions in which humans normally cycle through cooler nights and toastier daytimes.
The question, Evans says, is whether the immune response reflected in the new study is akin to one caused by a modest fever or a severe heat wave. “The outcome on the immune system will be quite different,” Evan says. The researchers were unable to pinpoint whether the heat exposure in the study was considered mild or hazardous for the Louisville residents. Riggs says that while all the blood draws occurred outside, the researchers didn’t track participants’ prior whereabouts. Participants could have spent most of their time before the procedure in the comfort of air-conditioning or outdoors under the full assault of the elements. Either case could influence the immune system and water down the strength of the biomarker correlations.
Still, the study hints at aspects of the immune system that might be most sensitive to climbing temperatures. Kristie Ebi, a University of Washington climate and health researcher, who wasn’t involved in the study, says the findings raise “interesting questions,” such as how strongly and quickly the body responds to heat. To find answers, researchers would need to carry out controlled animal studies in moderate heat-wave conditions and also monitor people’s blood signatures through the whims of the weather over multiple months. Such experiments could more convincingly tease out the nuances of how heat impacts the immune system’s sundry actors—and help provide better care for those who are most susceptible to these effects.
Certain demographics may be more vulnerable to the heat than others, especially those on medication, older adults and people with autoimmune conditions who can’t afford to push their overworked defensive system even more. Societal inequities, Ebi says, may also exacerbate heat’s pernicious effects—people living in urban heat islands or who lack access to air-conditioned infrastructure will more quickly feel the heat. One solution is to establish green spaces, which have been shown to reduce temperatures in heat islands and provide cooling shade. Riggs plans to use the results as a baseline to study whether tree-planting interventions in Louisville mitigate the hazards of heat waves.
As the planet hurtles toward global warming of 2.7 degrees F (1.5 degrees C) above preindustrial levels by midcentury, understanding how heat shapes the immune landscape is vital for preventing and treating heat stress in humans. “I think we’re just at the beginning of understanding what impact higher temperatures might have in terms of heat waves and patients,” Evans says.