What the science says about reducing fevers
You’re tired, achy, got the chills . . . and your temperature is rising. What to do? We can’t give you medical advice–please consult your trusted healthcare practitioner–but we can point you to some current published science so you can make an informed decision.
It is generally now understand that fever is good. Fever is your friend. It’s the immune system gearing up and taking action, and reducing it can slow recovery and increase severity. Fever can make you miserable though, so do explore your comfort options that don’t undermine the good work of a fever, such as the “wet sock therapy” that actually has science behind it.
The first paper in this list is very important because it shows that glutathione (GSH) depletion increases risk of severe outcome to viral infection. Glutathione is the body’s master antioxidant, vital for just about everything, and especially critical at times of illness. As Dr. Edward Fogarty puts it, “Precursors to GSH are anti-viral software for every cell.”
It is therefore critical to not administer products that reduce glutathione (acetaminophen/Tylenol) but instead attempt to INCREASE it. When you are well, you can do that through a diet rich in GSH precursors; in case of active infection, you may want to speed things up by increasing precursors through supplements. In the case of severe hospitalized patients, there are Tylenol-overdose protocols that work to recover the liver by administering GSH precursors.
Glutathione increase by the n‐butanoyl glutathione derivative (GSH‐C4) inhibits viral replication and induces a predominant Th1 immune profile in old mice infected with influenza virus
During aging, glutathione (GSH) content declines and the immune system undergoes a deficiency in the induction of Th1 response. Reduced secretion of Th1 cytokines, which is associated with GSH depletion, could weaken the host defenses against viral infections. We first evaluated the concentration of GSH and cysteine in organs of old mice; then, the effect of the administration of the N‐butanoyl GSH derivative (GSH‐C4) on the response of aged mice infected with influenza A PR8/H1N1 virus was studied through the determination of GSH concentration in organs, lung viral titer, IgA and IgG1/IgG2a production, and Th1/Th2 cytokine profile. Old mice had lower GSH than young mice in organs. Also the gene expression of endoplasmic reticulum (ER) stress markers involved in GSH metabolism and folding of proteins, that is, Nrf2 and PDI, was reduced. Following infection, GSH content remained low and neither infection nor GSH‐C4 treatment affected Nrf2 expression. In contrast, PDI expression was upregulated during infection and appeared counterbalanced by GSH‐C4. Moreover, the treatment with GSH‐C4 increased GSH content in organs, reduced viral replication and induced a predominant Th1 response. In conclusion, GSH‐C4 treatment could be used in the elderly to contrast influenza virus infection by inducing immune response, in particular the Th1 profile.
A Review of the Evidence Concerning Hepatic Glutathione Depletion and Susceptibility to Hepatotoxicity After Paracetamol Overdose
Paracetamol (acetaminophen) poisoning is common throughout the world. The management of nonstaggered (acute) paracetamol overdose is based on the plasma paracetamol concentration plotted on a treatment nomogram. In the UK there are two treatment lines on this nomogram, with the lower treatment line used for individuals felt to be at ‘high risk’ of paracetamol-related hepatotoxicity either as a result of induction of cytochrome P450 isoenzymes or reduction of intrahepatic glutathione. In this article we review the risk factors that, in current guidelines, are felt to increase risk due to a reduction in intrahepatic glutathione concentrations. Based on our review of the published literature, we feel that cystic fibrosis, acute viral illness, malnutrition, and eating disorders such as anorexia nervosa are likely to be associated with reduction in intrahepatic glutathione concentrations, and that this risk is likely to be related to malnutrition secondary to the disease. Chronic hepatitis C infection is also associated with reduced glutathione concentrations, although this appears to be independent of any associated malnutrition. Ageing and acute fasting are not associated with an increased risk of paracetamol-related hepatotoxicity due to reductions in glutathione concentrations. Finally, the evidence for HIV infection is inconclusive, particularly as the majority of studies were conducted in the pre-anti-viral treatment (HAART) era; however it is likely that patients with symptomatic HIV/AIDS have reduced glutathione concentrations due to associated malnutrition. Although there have been few studies which have specifically investigated whether there is an association between reduced intrahepatic glutathione concentrations and increased risk of paracetamol-related hepatotoxicity, in our opinion, it is likely that the above conditions that are associated with reduced glutathione concentrations, will be associated with an increased risk of paracetamol-related hepatotoxicity.
Bacterial- And Viral-Induced Inflammation Increases Sensitivity to Acetaminophen Hepatotoxicity
Acetaminophen (APAP)-induced hepatotoxicity accounts for nearly half of acute liver failure cases in the United States. The doses that produce hepatotoxicity vary considerably and many risk factors have been proposed, including liver inflammation from viral hepatitis. Interestingly, inflammatory stress from another stimulus, bacterial endotoxin (lipopolysaccharide, LPS), renders the liver more sensitive to hepatotoxicity from numerous xenobiotic agents. The purpose of these studies was to test the hypothesis that inflammation induced by LPS or infection with reovirus increases sensitivity to APAP-induced liver injury. For LPS-induced inflammation, C57BL/6J mice were treated with either saline or LPS (44 x 10(6) EU/kg, ip) 2 h before treatment with APAP (100-400 mg/kg, ip) or saline. No elevation in serum alanine aminotransferase (ALT) activity was observed in mice that received vehicle or LPS alone. LPS co-treatment produced a leftward shift of the dose-response curve for APAP-induced hepatotoxicity and led to significantly greater tumor necrosis factor-alpha (TNF) production than APAP alone. Reovirus serotype 1 (10(8) PFU, iv) induced inflammation in Balb/c mice as evidenced by increases in hepatic mRNAs for macrophage inhibitory protein-2, interleukin-6, and TNF. Co-administration of reovirus and APAP at doses of 450 and 700 mg/kg (2 h after reovirus) led to increases in serum ALT activity, whereas neither reovirus nor APAP alone produced liver injury. Consistent with the increases in serum ALT activity, histopathologic examination revealed centrilobular necrosis with marked neutrophilic accumulation only in livers of mice treated with LPS/APAP or with reovirus/APAP. The results suggest that normally noninjurious doses of APAP are rendered hepatotoxic by modest inflammation, whether bacterial or viral in origin.
Antipyretic drugs in patients with fever and infection: literature review
Background: antipyretic drugs are routinely administered to febrile patients with infection in secondary care. However, the use of antipyretics to suppress fever during infection remains a controversial topic within the literature. It is argued that fever suppression may interfere with the body’s natural defence mechanisms, and may worsen patient outcomes.
Method: a literature review was undertaken to determine whether the administration of antipyretic drugs to adult patients with infection and fever, in secondary care, improves or worsens patient outcomes.
Results: contrasting results were reported; two studies demonstrated improved patient outcomes following antipyretic administration, while several studies demonstrated increased mortality risk associated with antipyretics and/or demonstrated fever’s benefits during infection. Results also demonstrated that health professionals continue to view fever as deleterious.
Conclusion: the evidence does not currently support routine antipyretic administration. Considering patients’ comorbidities and symptoms of their underlying illness will promote safe, evidence-based and appropriate administration of antipyretics.
Effect of Antipyretic Therapy on the Duration of Illness in Experimental Influenza A, Shigella sonnei, and Rickettsia ricketts infections
Study Objectives. To determine whether antipyretic therapy prolongs the course of experimental influenza A, Shigella sonnei, and Rickettsia rickettsii infections.
Design. Retrospective observational study.
Setting. University Center for Vaccine Development.
Subjects. Fifty‐four volunteers with experimentally induced influenza A, 45 with S. sonnei, and 21 with R. rickettsii infections participated.
Interventions. Subjects from the six influenza A studies were challenged intranasally. If they met certain criteria, they were offered aspirin or acetaminophen for symptomatic relief. Subjects from the three Shigella studies were challenged with the bacteria and then given trimethoprim‐sulfamethoxazole. Acetaminophen also could be administered. In the one R. rickettsii trial, subjects were inoculated intradermally and treated with tetracycline. Again, acetaminophen was administered for symptomatic relief.
Measurements and Main Results. Data, excerpted from subjects’ study records, were evaluated using Wilcoxon tests, Spearman’s correlation coefficients, and multiple regression analysis. Two‐tailed hypotheses with a value of 0.05 were used for all of the analyses. There was a striking correlation between antipyretic therapy and duration of illness in subjects infected with influenza A and S. sonnei, but not R. rickettsii.
Conclusions. Multivariate analysis suggested that antipyretic therapy prolonged illness in subjects infected with influenza A, but its use was the result of prolonged illness in those infected with S. sonnei. The precise nature of these relationships requires a prospective, randomized, placebo‐controlled trial.
Adverse effects of aspirin, acetaminophen, and ibuprofen on immune function, viral shedding, and clinical status in rhinovirus-infected volunteers.
A double-blind, placebo-controlled trial was conducted to study the effects of over-the-counter analgesic/antipyretic medications on virus shedding, immune response, and clinical status in the common cold. Sixty healthy volunteers were challenged intranasally with rhinovirus type 2 and randomized to one of four treatment arms: aspirin, acetaminophen, ibuprofen, or placebo. Fifty-six volunteers were successfully infected and shed virus on at least 4 days after challenge. Virus shedding, antibody levels, clinical symptoms and signs, and blood leukocyte levels were carefully monitored. Use of aspirin and acetaminophen was associated with suppression of serum neutralizing antibody response (P less than .05 vs. placebo) and increased nasal symptoms and signs (P less than .05 vs. placebo). A concomitant rise in circulating monocytes suggested that the suppression of antibody response may be mediated through drug effects on monocytes and/or mononuclear phagocytes. There were no significant differences in viral shedding among the four groups, but a trend toward longer duration of virus shedding was observed in the aspirin and acetaminophen groups.
Acetaminophen: More harm than good for chickenpox?
Study objective To determine whether acetaminophen affects the duration or severity of childhood varicella.
Design: Randomized, double-blind, placebo-controlled trial.
Setting: Office- and hospital-based pediatric practices.
Patients: Seventy-two children between 1 and 12 years of age entered the study. One child was withdrawn because of high fever, and three children did not complete the study; 31 received placebo and 37 received acetaminophen.
Interventions: Acetaminophen, 10 mg/kg/dose, was given at 8 am, 12 pm, 4 pm, and 8 pm for 4 days. Placebo was given to the control group. Itching, appetite, activity, and overall condition were measured for 6 days. The time to last vesicle formation, time to total scabbing, and time to total healing were measured until complete resolution of the exanthem.
Measurements and main results: The following results were better in the placebo group (p<.05): time to total scrabbing 5.6 days (SD 2.5) versus 6.7 days (SD 2.3) in the acetaminophen group, and itching on day 4 in the placebo group (symptom score 2.9 (SD 0.20) vs 2.2 (SD 0.26)). Activity was better in the acetaminophen group on day 2 (3.13 (SD 0.23) vs 2.82 (SD 0.24))
Conclusions: These results provide evidence that acetaminophen does not alleviate symptoms in children with varicella and may prolong illness.