The Roman Celsus in the 1st century A.D. identified four classical signs of inflammation: Calor, dolor, rubor, and tumor; these are heat, pain, redness, and swelling. Some of the most annoying symptoms of influenza, for instance, involve vascular congestion of mucous membranes, from increased blood flow leading to tissue swelling (tumor), increased warmth and fever (calor). A new study suggests that calor is critically important in fighting viral infections that affect the joints.
Chikungunya is a tropical disease that causes debilitating joint pain, among other distressing symptoms. It is spreading rapidly in the Caribbean and North America, partly because of favorable mosquito habitat and warming temperatures that give the virus ample opportunities for transmission. Remarkably, I have had two patients with acute Chikungunya in Albuquerque New Mexico. One had returned from St. Maarten, and the other had attended a conference in Orlando, Florida.
Suhrbier’s group was interested in a pattern of arthritis caused by Chikungunya virus (CHIKV). The arthritis, lasting weeks to months, is most severe in the hands and feet of victims. In the study, mice were inoculated with CHIKV and then housed at a warmer than usual temperature “30°C rather than the conventional 22°C, with the feet of the former mice being ≈3–4°C warmer.”
The warm-footed mice – housed at 30°C – had less foot swelling and lower viremia (fewer circulating viruses in the blood) as compared to the mice kept at the regular temperature.
The effect was found to be due to a more vigorous immune response – more interferon production – in the warm-footed mice. The authors conclude that the virus attacks joints in the distal extremities (hand and feet) in part because the temperature at those sites is lower than the core body temperature.
I took another takeaway from this study. When we see joint redness – which is pretty much an everyday event in the ER – what we are seeing is a localized fever.
This common response delivers increased blood flow, increased immune cells, and increased temperature to the joint, and it is likely to combat infection in case of viral arthritis.
How about nose fevers? Nasal congestion has the same effect when we get a cold, increasing the tissue temperature in the nose.
The temperature of air in the nose is an important risk factor for infection by rhinoviruses, the organism causing the common cold. Carl Zimmer’s described Akiko Iwasaki’s work on temperature and rhinovirus infection some time ago in The New York Times. Iwasaki showed that cold temperature impairs cellular immunity and facilitates infection by the virus. The study’s author also suggests that fever is beneficial in preventing further infection by the virus.
So, if cold air and tissues in the nose are an Achilles heel for us, allowing easy infection by rhinoviruses, does inflammation in the nose generate a localized fever that protects us?
A combination of a local defenses and body-wide defenses might be important in fighting infection. We covered this hypothesis several times on this blog, e.g here and here. Ed LeGrand and I have written about the host defense function of fever as a stress that harms invaders more than ourselves. LeGrand followed up with another study modeling the effect of combined stresses, like local warmth and systemic fever. The combination of local elevated temperature and systemic fever were better than either one alone in defeating infections. You can read their work here: Synergy of local, regional, and systemic non-specific stressors for host defense against pathogens.
As a final thought, cold air induces rhinorrhea (runny nose) in many people even in the absence of infection. This vasomotor rhinorrhea involves tissue edema and increased blood flow. Maybe cold rhinorrhea prevents viral infections from getting established by raising the temperature. If this is true, taking cold and allergy medications that prevent Celsus’s dolor, tumor, and calor might do more harm than good.
Copyright © Joe Alcock MD
Come this summer to the 4th annual meeting of ISEMPH – The International Society for Evolution, Medicine and Public Health in beautiful Park City, Utah. Registration and abstract submissions open soon!
Emergency Physician, Educator, Researcher, interested in the microbiome, evolution, and medicine