Home testing: friend or foe?

Though more patients seek out home tests, nurses find pros and cons associated with their use.     

Inflammasome: Cancer's friend or foe?

High serum concentrations of IL-1β and IL-18 are correlated to malignancies with low-rate survival from the time of diagnosis. The multimeric complex of the inflammasome is responsible for IL-1β/IL-18 synthesis/release. A number of endogenous (damage-associated molecular patterns) and exogenous (pathogen-associated molecular patterns) stimuli can provide signals for inflammasome activation in cancer. These stimuli can behave as tumor promoters via inducing chronic inflammation that, rather than providing a protective response to loss of tissue homeostasis, aberrantly facilitates tumor development. This view is contrasted in animal models of colon cancer in which the activation of some inflammasome complexes is associated with tumor protection. More studies are needed to understand the biology of the inflammasome in cancer and explore its therapeutic potential.     

CD8+ T cells in asthma: friend or foe?

While it is well established that CD4(+) T lymphocytes play a crucial role in the initiation, progression and persistence of asthma, the role of CD8(+) T cells is less understood. CD8(+) T cells form functionally similar subsets which exhibit similar cytokine profiles as Th1 and Th2 cells, known as Tc1 and Tc2. Evidence from animal studies suggest that CD8(+) T cells are capable of regulating IgE production through the induction of IL-12 and IL-18 production in dendritic cells, and that CD8(+) T cells may act to moderate Th2 polarisation within the localised lymph nodes during allergic sensitisation. Such findings have led to the suggestion that Th1 polarising, CD8(+) T cell-inducing vaccines would inhibit the development of airway hyperresponsiveness (AHR) and Th2 cell infiltration. Despite these positive findings, the role of CD8(+) T cells within the lung remains poorly understood. While CD8(+) T cells, particularly those expressing the Tc1 phenotype, are capable of moderating inflammation and suppressing AHR, it has been postulated that Tc2 CD8(+) T cells predominate within established asthma and may act to amplify the inappropriate immune response which defines the condition. Within the clinic, the association between CD8(+) T cells and asthma is almost universally defined as injurious, further suggesting a prejudicial role for these cells within the established disease. CD8(+) T cells may be a valuable potential target for therapeutic intervention, either by potentiating their regulatory effects prior to the development of sensitisation, or through suppressing their pro-inflammatory properties within established atopy.     

Complement in atherosclerosis: friend or foe?

Summary. Atherosclerosis is a chronic inflammatory disease and the complement system plays a central role in innate immunity. Increasing evidence exists that the complement system is activated within atherosclerotic plaques. However, the role of complement in atherogenesis is not fully understood. Whereas complement activation by the classic and lectin pathway may be protective by removing apoptotic cells and cell debris from atherosclerotic plaques, activation of the complement cascade by the alternative pathway and beyond the C3 convertase with formation of anaphylatoxins and the terminal complement complex may be proatherogenic and may play a role in plaque destabilization leading to its rupture and the onset of acute cardiovascular events. In this review article we present evidence for complement activation within atherosclerotic plaques and we discuss recent data derived from experimental animal models that suggest a dual role of complement in the development of the disease. In addition, we summarize the role of complement components as biomarkers for cardiovascular disease.     

Prostate-specific antigen screening: friend or foe?

Prostate cancer is the most frequently diagnosed cancer among men in the United States. The prostate-specific antigen (PSA) blood test is the most commonly utilized test to detect early prostate malignancy. Elevated PSA levels suggest to providers the possibility that their patients are at a higher statistical risk of harboring asymptomatic, organ-confined prostate cancer. Although PSA testing has become a primary screening method for prostate cancer in the United States, this test has come under scrutiny. PSA screening lacks a high level of specificity due to frequent false-positive results. Additionally, major health organizations differ in their screening recommendations for use of the PSA test. However, the medical community, and more importantly, patients, must understand the benefits and possible detriments of this screening test. Providers should approach each man individually when recommending a PSA test, noting that many risk factors must be considered in a screening protocol for prostate cancer.     

Immunomodulatory effects of caffeine: friend or foe?

Caffeine is a member of the methylxanthine family of drugs, and is the most widely consumed behaviourally active substance in the western world. This article is focused on the impact of caffeine on immune function. In this regard, a number of in vitro and in vivo studies have demonstrated that caffeine modulates both innate and adaptive immune responses. For instance studies indicate that caffeine and its major metabolite paraxanthine suppress neutrophil and monocyte chemotaxis, and also suppress production of the pro-inflammatory cytokine tumour necrosis factor (TNF)-alpha from human blood. Caffeine has also been reported to suppress human lymphocyte function as indicated by reduced T-cell proliferation and impaired production of Th1 (interleukin [IL]-2 and interferon [IFN]-gamma), Th2 (IL-4, IL-5) and Th3 (IL-10) cytokines. Studies also indicate that caffeine suppresses antibody production. The evidence suggests that at least some of the immunomodulatory actions of caffeine are mediated via inhibition of cyclic adenosine monophosphate (cAMP)-phosphodiesterase (PDE), and consequential increase in intracellular cAMP concentrations. Overall, these studies indicate that caffeine, like other members of the methylxanthine family, is largely anti-inflammatory in nature, and based on the pharmacokinetics of caffeine, we suggest that many of its immunomodulatory effects occur at concentrations that are relevant to normal human consumption. Finally, the potential of caffeine-induced immunomodulation to significantly impact upon health and well-being are discussed.     

Chemotherapy: friend or foe to cancer vaccines?

Cancer vaccines are on the threshold of taking their place alongside the more traditional cancer treatment modalities of surgery, radiation therapy and chemotherapy. The toxicology and immunopharmacology of therapeutic cancer vaccines, particularly those that secrete granulocyte macrophage colony stimulating factor (GM-CSF), are currently under active clinical investigation. Interestingly, drugs traditionally used for tumor cytoreduction can have both positive and negative effects on host immunity. Exploration of the potential pharmacodynamic interactions of antineoplastic drugs with GM-CSF-secreting vaccines has revealed that low doses of some chemotherapeutics can augment the antitumor immunity induced by GM-CSF-secreting vaccines. These interactions will require thorough preclinical evaluation to maximize the clinical impact of this type of therapeutic cancer vaccine.     

Doppler ultrasound and D-dimer: friend or foe?

The diagnosis of venous thromboembolism has evolved considerably with the development of standardized diagnostic algorithms that include clinical probability assessment, D-dimer measurement and the use of non-invasive imaging modalities such as compression ultrasonography and computed tomography angiography. The implementation of these strategies aims to improve resource allocation and patient outcome. The judicious use of these diagnostic tools requires a thorough knowledge of the appropriate clinical setting in which every test and strategy is efficient and can be used safely. For this purpose, D-dimer measurement and compression ultrasonography are complementary: the former is mainly used to exclude VTE in selected patients, while the latter is used to confirm the presence of an underlying DVT. This review provides an appraisal of the features and use of D-dimer and compression ultrasonography in the context of suspected venous thromboembolism.