The acute stress response is characterized by activation of multiple interconnected systems in the body, resulting in the release of a flood of hormones and immune mediators into circulation. In addition to detection of these molecules in the serum, saliva can serve as a source of these markers as well and can be collected in a non-invasive way. The complete profile of salivary biomarkers associated with the hypothalamic pituitary adrenal/gonadal axes and the immune system during the acute stress response has not been fully elucidated. In a cohort of 62 first responders engaged in a stress training exercise, we set out to determine patterns of cytokine, chemokine and hormone shifts during the acute stress response. Salivary samples were collected immediately before (pre-stress), immediately after (post-stress) and 1 h after the stress test (recovery). Multiplex ELISA panels of 42 cytokines and 6 steroid and thyroid hormones were used to determine concentrations of these biomarkers during the three aforementioned time points. Principal components analysis was conducted to determine patterns in the large data sets collected. In our ≥0.3 loading principal components analysis, for pre-stress vs. post, post-stress vs. recovery and pre-stress vs. recovery, a total of three, four and three factors accounted for 56.6, 68.34, and 61.70% of the biomarker variation for each phase respectively. In the ≥0.7 loading principal components analysis, three, four and three factors were found for pre-stress vs. post, post-stress vs. recovery and pre-stress vs. recovery stages, respectively. Of note, in our ≥0.3 loading principal components analysis, MCP1 was present in all three factors from pre-stress to post-stress, and fractalkine was found to be in all four factors post-stress vs. recovery and pre vs. recovery from stress. Additionally, hormones testosterone, estradiol, T4 and T3 grouped together consistently in the same factor for all phases of acute stress in both ≥0.3 and ≥0.7 principal components analysis. Overall, our results identified specific patterns of immune markers and hormones that shift during acute stress and warrant further investigation to understand their mechanistic role in regulating the stress response.

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Despite advances in antimicrobial therapy and even the advent of some effective vaccines, Pseudomonas aeruginosa (P. aeruginosa) remains a significant cause of infectious disease, primarily due to antibiotic resistance. Although P. aeruginosa is commonly treatable with readily available therapeutics, these therapies are not always efficacious, particularly for certain classes of patients (e.g., cystic fibrosis (CF)) and for drug-resistant strains. Multi-drug resistant P. aeruginosa infections are listed on both the CDC’s and WHO’s list of serious worldwide threats. This increasing emergence of drug resistance and prevalence of P. aeruginosa highlights the need to identify new therapeutic strategies. Combinations of monoclonal antibodies against different targets and epitopes have demonstrated synergistic efficacy with each other as well as in combination with antimicrobial agents typically used to treat these infections. Such a strategy has reduced the ability of infectious agents to develop resistance. This manuscript details the development of potential therapeutic targets for polyclonal antibody therapies to combat the emergence of multidrug-resistant P. aeruginosa infections. In particular, potential drug targets for combinational immunotherapy against P. aeruginosa are identified to combat current and future drug resistance.

Thygeson superficial punctate keratitis (TSPK) is clinically characterized by exacerbations and remissions of gray-white opacities within the corneal epithelium, most often bilateral but may be asymmetric. Symptoms typically include photophobia, tearing, blurring, and eye irritation. Although disease progression and prognosis are well described, the exact cause is unknown. Hypotheses exist implicating virus-mediated immunity as the cause of TSPK following cases of viral keratitis; however, several polymerase chain reaction studies refute the infectious process concurrently with symptomatic TSPK. This is further supported by the consistent lack of response to antiviral and antibacterial treatment. A subset of dendritic cells known as Langerhans cells (LC) found within the corneal epithelium has been positively correlated with exacerbations of TSPK. Langerhans cells proliferate to protect and mitigate the cornea's inflammatory response, but the inflammatory triggers and relapses associated with TSPK are not well understood. Several topical drugs exist to treat inflammation related to TSPK; however, drug delivery is a major barrier to treatment because of the tear film and epithelial barrier. Drug-eluting contact lenses that target intermediates of inflammation could serve as a more effective treatment modality because of the increased bioavailability of the drugs. This review is an in-depth survey of the literature regarding the relationship between the origin and pathophysiology of LC and TSPK at the immunologic level. We also discuss potential pharmacotherapeutic interventions for TSPK prevention and treatment.