A study carried out in monkeys has found that long-term alcohol consumption can affect the turnover of immune system cells in the intestine, and the depletion of these cells by simian immunodeficiency virus (SIV). The study’s findings were published in the 15th April edition of The Journal of Acquired Immune Deficiency Syndromes.
Although studies have not examined any similar effects of alcohol and HIV on immune cells in humans, these results suggest that long-term intake of large amounts of alcohol may affect the activity of the immune system during early HIV infection. This, in turn, may cause higher viral loads by increasing HIV replication.
Researchers in the United States recently discovered that giving rhesus macaques alcohol over an extended period caused higher levels of SIV replication and higher viral loads in the blood. The monkeys also had higher levels of CD4 T-cells in the intestine, as well as low levels of CD8 T-cells, which are responsible for detecting and killing infected cells in the body.
To work out whether these observations were related, the group of investigators went on to examine the effects of alcohol on immune cells in the blood, lymph nodes and intestine. By comparing the proportions of different types of lymphocytes, they discovered that changes in the immune system in the intestine may be responsible for higher viral loads in the blood.
The investigators gave alcohol to eleven macaques through a stomach tube on four days of every week. The dose of alcohol was designed to mimic ‘binge-drinking’ sessions, with a 30-minute infusion at a high rate, followed by four and a half hours of slower infusion. This maintained blood alcohol levels between 0.23 and 0.27%, which is equivalent to very serious intoxication in humans: in the United Kingdom the legal limit for driving is 0.08%.
After eight weeks, there were no differences in the types of lymphocyte found in the blood or lymph nodes of these monkeys, compared to a group of eleven monkeys given sugar infusions containing the same amount of calories as the alcohol infusions.
In contrast, samples of intestine from the monkeys given alcohol contained higher levels of ‘naive’ and ‘central memory’ CD4 T-cells. Naive CD4 T-cells have not yet been activated by a foreign substance, while central memory CD4 T-cells are responsible for protecting the body against foreign organisms that the body has already been exposed to.
The investigators also found that the monkeys given alcohol had lower levels of ‘effector memory’ CD8 T-cells in the intestine. These cells are responsible for the rapid identification and killing of cells infected with organisms the body has already encountered.
The investigators went on to infect seven of the alcohol-treated and eight of the sucrose-treated macaques with SIV, by injecting it into the rectum. All of the monkeys became SIV-positive, with peak viral loads after 14 to 21 days.
As in the investigators’ previous studies, the monkeys being treated with alcohol had higher viral loads than those treated with sucrose three to six weeks after infection. However, the two groups had similar viral loads after this time point. CD4 cell counts in the blood declined at similar rates in the two groups, and none of the animals had symptoms of SIV infection when the samples were taken.
As expected, the CD4 T-cells in the intestine were depleted in the infected monkeys eight weeks after infection.
However, despite having higher levels before infection with SIV, the macaques treated with alcohol showed a depletion of central memory cells in the intestines after infection. They also had higher levels of SIV in the intestine, lymph nodes and spleen. In contrast, the sucrose-treated monkeys did not have a significant decrease in central memory cells.
Both groups showed depletion of these cells in the lymph nodes, and of effector memory cells in the intestine.
The investigators conclude that alcohol increases the number of the major target cells for SIV in the intestine, and that this allows replication to be enhanced in these animals.
“Chronic alcohol consumption results in significantly increased percentages of central memory CD4 T-cells in the intestine of macaques”, they write. “[This] strongly suggests that increased levels of these optimal viral target cells is a major reason for increased replication of SIV in alcohol-fed macaques.
“These results point towards an overall adverse effect of chronic alcohol consumption on the intestinal mucosal immune compartment,” they add.
The researchers find it difficult to explain the reasons for alcohol’s effect on intestinal immune cells. However, they provide some evidence that alcohol could inhibit the turnover of T-cells, resulting in the altered proportions of the different cell types. Although it remains to be proven, they suggest that this increases the availability of naïve and central memory T-cells in which SIV can replicate.
“Alcohol consumption results in a disturbance in intestinal lymphocyte cycling or turnover and / or affects the normal conversion of naïve to activated / memory cells,” they explain, “resulting in significantly higher percentages of naïve lymphocyte subsets in the intestines and lymph nodes.”
Poonia B et al. Intestinal lymphocyte subsets and turnover are affected by chronic alcohol consumption: implications for SIV / HIV infection. J Acquir Immune Defic Syndr 41: 537-547, 2006.