Immunomodulation by tramadol combined with acetaminophen or dexketoprofen: In vivo animal study.

Among other functions, macrophages remove foreign particles, including medications, from the circulation, making them an important target for immunomodulatory molecules. Currently, growing evidence suggests that analgesics affect the activity of immune cells not directly related to pain, and thus may induce unwanted immunosuppression in patients at risk. However, the immunomodulatory effects resulting from macrophage targeting by these drugs are understudied. Therefore, the current study investigated the immune effects induced in healthy mice by repeated administration of tramadol alone or in combination with acetaminophen or dexketoprofen. We observed that drug administration decreased the percentage of infiltrating macrophages in favor of resident macrophages in peritoneal exudates. While all drugs reduced the number of infiltrating macrophages that phagocytosed sheep red blood cells (SRBC), their administration increased the effectiveness of phagocytosis, and treatment with acetaminophen with or without tramadol elevated the expression of MHC class II by Mac3+ macrophages. Interestingly, SRBC-pulsed macrophages from mice treated with tramadol combined with acetaminophen potently activated SRBC-specific B cells in humoral response, and administration of these drugs to recipients of contact hypersensitivity effector cells augmented the resulting cellular immune response. In addition, tramadol administered alone or with dexketoprofen enhanced the spontaneous release of pro-inflammatory cytokines by macrophages. Our current research findings demonstrate that tramadol therapy in combination with acetaminophen or dexketoprofen has a relatively low risk of causing immunosuppressive side effect because the drugs slightly reduce the inflammatory reaction of macrophages but do not impair their ability to activate the adaptive immune responses.

The CD36 and SR-A/CD204 scavenger receptors fine-tune Staphylococcus aureus-stimulated cytokine production in mouse macrophages.

The occurring in SR-A/CD204- or CD36-deficient mice increased susceptibility to infections with Staphylococcus aureus (Sa) had traditionally been ascribed to the impairment of macrophage-mediated phagocytosis, which is, however, inconsistent with low effectiveness of unopsonized Sa killing within macrophages and redundant roles of both receptors in this process. We have found that Sa-stimulated cytokine production in mouse macrophages seems to be exclusively mediated by TLR2, mainly from within endosomes in response to Sa-derived lipoteichoic acid. By driving endocytic trafficking of TLR2 and its ligands through the clathrin-dependent pathway, CD36 and SR-A sensitize macrophages to activation by Sa as well as regulate the type and amount of cytokines produced. Additionally, upon direct Sa binding, both receptors autonomously generate anti-inflammatory signaling. Consequently, the delayed induction of acute inflammation in knockout mice may allow for the initial, uncontrolled multiplication of bacteria, stimulating excessive, septic shock-inducing production of inflammatory cytokines in later stages of infection.

Incidence of Vaccine-Preventable Childhood Diseases in the European Union and in the European Free Trade Association Countries.

INTRODUCTION: Despite the widespread availability of vaccines, the incidence of vaccine-preventable childhood diseases (VPCD) started to grow in recent years. The aim of the study was to compare the annual incidence of selected VPCDs in the EU (European Union) and EFTA (European Free Trade Association) countries in the period of the last 5 years (2014-2019 or other intervals, depending on data availability), and the country-specific vaccine schedules. METHODS: VPCD incidence rates in Europe were based on "The Surveillance Atlas of Infectious Diseases" by the ECDC (European Centre for Disease Prevention and Control); vaccination schedules were based on ECDC reports. RESULTS: The obligation to vaccinate was not universal, and it generally only applied to two preparations: the MMR (measles, mumps, rubella) vaccine and the one against polio. During the study, the situation associated with mumps did not change or improve in individual countries; the median incidence amounted to 30 cases. The median incidence associated with rubella amounted to 1 case, but in a few countries, it grew very rapidly, i.e., in Germany, Italy, and Romania; in Poland, the incidence was clearly decreasing, from 5923 to 1532 cases. The most dynamic situation concerned measles. The total median was 2.4 cases per 100,000 population; the only one country with falling incidence was Germany. The diseases associated with Streptococcus pneumoniae and Neisseria meningitidis remained at a stable level in all analyzed countries. CONCLUSION: Vaccine schedules differ among the countries, so does the epidemiological situation of selected diseases. Morbidity on measles was the most disturbing phenomenon: the incidence rate increased in almost 40% of all countries, regardless of the obligation to vaccinate. The increasing incidence of VPCD may be due to anti-vaccine movements, the activity of which is often caused by mistrust and spreading misinformation. In order to better prevent the increase in morbidity, standardization of vaccine schedules and documentation should be considered in the EU countries.