Inflammation and its discontents
When cells of the immune system encounter invading germs they can become activated and enter into a heightened state of alert. Such cells help to marshal the immune system against germs. Here is a greatly simplified response by the immune system to an infection:
- Chemical signals are released that attract other cells of the immune system with specialized functions to where the invading germs are concentrated.
- As the number of immune system cells increases at the site of infection, some of these cells try to contain the germs.
- Other cells take a molecular picture of the invading germ and then travel to lymph nodes and lymphatic tissues where they warn the immune system about the invader.
- As a result of these actions, the immune system becomes activated and lymph nodes and lymphatic tissues make many copies of CD8+ cells—the body’s premier infection-fighting cells. These CD8+ cells are released into circulation to attack germs and kill infected cells.
- The body raises its temperature to try to kill germs.
- Usually all of these immune responses help to contain an infection, and as the number of germs decreases, the immune system releases anti-inflammatory signals and other cells that specialize in suppressing the immune system to dampen its responses.
However, when the immune system is not able to control and vanquish an infection, a state of activation persists. We discuss the consequences of this persistent activation later in this article.
Where is the immune system?
The immune system is located in several organs and tissues such as the thymus gland, spleen and bone marrow. There are also many lymphatic tissues and lymph nodes scattered throughout the body between the neck and the knees, particularly around the intestines. Also, cells of the immune system are distributed throughout the body and found in other major organ-systems, including the brain, heart and blood vessels, kidneys, liver, lungs and so on. The emplacement of cells of the immune system in these different organ-systems serves to provide local protection for them.
In cases of chronic infection when the immune system remains activated, its inflamed cells release chemical signals that in turn cause inflammation in the organ-systems where they are resident. Thus, inflammation is transferred to other parts of the body. Temporary inflammation during short-lived infections is useful for marshalling the immune response and nutrients to feed the creation of millions (perhaps even billions in some cases) of new cells. However, chronic inflammation from ongoing infection—such as that arising from HIV—can injure organ-systems, causing them to slowly degrade.
Researchers are finding that in HIV-negative people excessive levels of inflammation appear to play a role in the injury associated with many health conditions, and perhaps even in the cause of some conditions, including the following:
- cardiovascular disease
- higher-than-normal blood pressure
- thinning bones
It is possible that inflammation may also play a role in HIV-positive people when the above-listed conditions occur.
Studies have found that taking combination anti-HIV therapy (commonly called ART or HAART) greatly reduces the level of HIV-related inflammation. However, because ART does not cure HIV infection, some degree of excess inflammation persists. Scientists are therefore conducting studies to try to find ways to safely suppress the excess inflammation that occurs in HIV-positive people
In this issue, we review some studies that explore ways to help dampen HIV-related inflammation among ART users. Future issues of TreatmentUpdate will also report on HIV-related inflammation.
—Sean R. Hosein
- Vassileva V, Piquette-Miller M. Inflammation: the dynamic force of health and disease. Clinical Pharmacology and Therapeutics. 2014 Oct;96(4):401-5.
- Pawelec G, Goldeck D, Derhovanessian E. Inflammation, ageing and chronic disease. Current Opinion in Immunology. 2014 Aug;29:23-8.
- Lashinger LM, Rossi EL, Hursting SD. Obesity and resistance to cancer chemotherapy: interacting roles of inflammation and metabolic dysregulation. Clinical Pharmacology and Therapeutics. 2014 Oct;96(4):458-63.
- Bettcher BM and Kramer JH. Longitudinal inflammation, cognitive decline, and Alzheimer’s disease: a mini-review. Clinical Pharmacology and Therapeutics. 2014 Oct;96(4):464-9.
- Saracino A, Bruno G, Scudeller L, et al. Chronic inflammation in a long-term cohort of HIV-infected patients according to the normalization of the CD4:CD8 ratio. AIDS Research and Human Retroviruses. 2014; in press.
- Kooman JP, Kotanko P, Schols AM, et al. Chronic kidney disease and premature ageing. Nature Reviews Nephrology. 2014; in press.
- S Metkus T Jr, Brown TT, S Post W, et al. Cardiovascular disease associated with the human immunodeficiency virus: an update. Current Treatment Options in Cardiovascular Medicine. 2014 Nov;16(11):346.
- d’Ettorre G, Ceccarelli G, Giustini N, et al. Taming HIV-related inflammation with physical activity: a matter of timing. AIDS Research and Human Retroviruses. 2014 Oct;30(10):936-44.
- Anzinger JJ, Butterfield TR, Angelovich TA, et al. Monocytes as regulators of inflammation and HIV-related comorbidities during cART. Journal of Immunological Research. 2014;2014:569819.
- De Pablo-Bernal RS, Ruiz-Mateos E, Rosado I, et al. TNF-α levels in HIV-infected patients after long-term suppressive cART persist as high as in elderly, HIV-uninfected subjects. Journal of Antimicrobial Chemotherapy. 2014 Nov;69(11):3041-6.
- Seddiki N, Brezar V, Draenert R. Cell exhaustion in HIV-1 infection: role of suppressor cells. Current Opinion in HIV/AIDS. 2014 Sep;9(5):452-8.
- Poudel-Tandukar K, Bertone-Johnson ER, Palmer PH, et al. C-reactive protein and depression in persons with Human Immunodeficiency Virus infection: The Positive Living with HIV (POLH) Study. Brain, Behaviour and Immunity. 2014; in press.
- Hileman CO, Labbato DE, Storer NJ, et al. Is bone loss linked to chronic inflammation in antiretroviral-naive HIV-infected adults? A 48-week matched cohort study. AIDS. 2014 Jul 31;28(12):1759-67.
- Tsoukas C. Immunosenescence and aging in HIV. Current Opinion in HIV/AIDS. 2014 Jul;9(4):398-404.
- Wilson EM, Singh A, Hullsiek KH, et al. Monocyte-activation phenotypes are associated with biomarkers of inflammation and coagulation in chronic HIV infection. Journal of Infectious Diseases. 2014 Nov 1;210(9):1396-406.
- Masiá M, Robledano C, Ortiz de la Tabla V, et al. Coinfection with human herpesvirus 8 is associated with persistent inflammation and immune activation in virologically suppressed HIV-infected patients. PLoS One. 2014 Aug 18;9(8):e105442.
- Cockerham LR, Jain V, Sinclair E, et al. Programmed death-1 expression on CD4⁺ and CD8⁺ T cells in treated and untreated HIV disease. AIDS. 2014 Jul 31;28(12):1749-58.
- Mandell DT, Kristoff J, Gaufin T, et al. Pathogenic features associated with increased virulence upon Simian immunodeficiency virus cross-species transmission from natural hosts. Journal of Virology. 2014 Jun;88(12):6778-92.
- Pedersen KK, Manner IW, Seljeflot I, et al. Monocyte activation, but not microbial translocation, is independently associated with markers of endovascular dysfunction in HIV-infected patients receiving cART. Journal of Acquired Immune Deficiency Syndromes. 2014 Dec 1;67(4):370-4.