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Infections in older individuals can result in cognitive function decline, yet research is limited on how recurrent infections affect cognitive responses. Activation of the immune system results in sickness responses mediated by cytokines. This pilot study examined effects of a model of recurrent infection in aged, male Brown Norway rats on sickness responses, including spatial learning, and cytokine levels. To model initial and recurrent infection, 300 μg/kg lipopolysaccharide (LPS) or saline was administered 1/day for 2 consecutive days during 2 weeks separated by 16 days. Testing occurred for 6 days during each LPS injection week using the Morris water maze, a measure used to evaluate spatial learning. Directional heading error (DHE) and swim time latency served as spatial learning indices. Retention tests and probe trials assessed memory. Plasma cytokine levels were assessed 5 and 24 hr after each LPS injection during Week 2. While food intake and weight decreased significantly in LPS-injected rats compared to controls during Week 1, both displayed increased DHE. Despite exhibiting lessened sickness behaviors during Week 2, experimental animals still displayed spatial learning deficits. Probe trials revealed memory deficits in LPS-injected animals. Interleukin 6 level was higher in the experimental group 5 and 24 hr after LPS injection on Day 1 compared to Day 2 and higher in the experimental compared to the control group at 5 hr on Day 1. Cognitive effects were dissociated from metabolic effects in aged rats, with recurring LPS exposure resulting in persistent cognitive impairment despite decreased sickness responses. Further research with older individuals is warranted.

Objective: Immune challenges result in sickness responses such as decreased activity, fever, and spatial learning deficits. While these responses occur simultaneously, they are not usually evaluated concurrently or for an extended time. The purpose of this study was to examine how an immune challenge affected activity and temperature responses in animals tested concurrently in the Morris water maze (MWM) over 5 days and how aging interacts with such responses., Method: An accepted model of aging, adult ( n = 10; 5-6 months) and aged ( n = 7; 22 months) male Brown-Norway rats were implanted with a telemetry device (Mini Mitter, Oakmont, PA) to continuously monitor temperature and activity following an immune challenge. These animals were injected with either 250 μg/kg lipopolysaccharide (LPS) or 0.9% sodium chloride and then assessed in the MWM for 5 days., Results: Temperature responses varied by age. Initial temperatures decreased in both experimental groups followed by an increase (fever) in the adult group, while the temperatures of the aged animals remained decreased. Although both age groups were sedentary at baseline, activity decreased after LPS only in the adult group., Conclusion: An LPS immune challenge resulted in age-dependent temperature and activity changes. There was an absence of fever and no effect on activity in aged LPS-treated animals. These results may suggest the need to assess a broader spectrum of sickness responses when monitoring elderly individuals for infection and not rely on the presence of fever. Activity may not be a sensitive indicator of sickness in some aging models.

Sickness behaviors, adaptive responses to infections, include lethargy, depression, reduced eating and grooming, and concentration problems resulting from interactions between the immune and neuroendocrine systems. Detecting these responses is especially critical in the elderly, as the infections that cause them can lead to cognitive impairment. While deficits in spatial learning, a hippocampal-dependent form of learning, are part of the sickness response, directional heading errors (DHEs; an indicator of spatial-learning deficits) and their time trajectories need further examination. Therefore, we simultaneously investigated the time trajectory of age-dependent sickness responses and spatial learning over 5 days in adult (5-6 months) and aged (22 months) male Brown-Norway rats injected with 250 μg/kg lipopolysaccharide (LPS; experimental group) or 0.9% sodium chloride (control group). LPS administration resulted in pronounced, age-dependent weight loss and decreased food intake that persisted in the aged group. Animals were tested for 5 days (trial) in the Morris water maze. After 7 days of rest, animals were retested for 2 days (retention). Adult and aged LPS-treated animals displayed greater differences in mean DHE than the control groups, indicating that they exhibited more DHE over the trial days. Experimental groups did not show consistent DHE improvement until Day 4 (adult) or 5 (aged). LPS had no effect on probe or retention trials. We conclude that LPS activation of the immune system results in a selective, age-dependent impairment in spatial learning, decreased food intake, and weight loss. All of these results are prolonged in aged animals.

Purpose: This report extends the findings of a prior study comparing the level of plasma cytokines in women with breast cancer to those of women with a benign breast biopsy with the addition of a normal comparison group. The results of this three-group comparison are presented as background for discussing several methodologic challenges for biobehavioral research in inflammatory-based conditions., Method: This study used a descriptive, cross-sectional design to compare the levels of plasma cytokines in women with breast cancer, women with a benign breast biopsy, and a normal comparison group. The levels of 17 cytokines were measured using multiplex bead array assays (Bio-Plex®). Data analysis included a variety of descriptive and graphical techniques to illustrate between-group differences in cytokine profiles., Results: The levels of plasma cytokines in the sample of 35 women who had recently been diagnosed with breast cancer, 24 women with a suspicious breast mass, who subsequently were found to have a benign breast biopsy, and 33 women in a normal comparison group present a background for discussing the implications of extreme between-group differences for biobehavioral nursing research. Both the levels of individual cytokines and their patterns were distinctly different in the three groups., Conclusion: The exemplar presented from the three-group comparison has implications for planning biobehavioral nursing research in patients with conditions characterized by inflammation.

Multiple concurrent symptoms are highly prevalent in patients with cancer. However, little is known about the relationships among these symptoms and their underlying mechanisms. A number of cytokines that are involved in the development of sickness behavior are hypothesized to be a mechanism for symptom clusters. Measurement of these cytokines would provide valuable information that could be used to elucidate mechanisms underlying the development of symptom clusters and the identification of potential targets for intervention studies. In this article, the authors explore several issues that warrant careful consideration when designing a research study involving the use of a cytokine as a biomarker in symptom cluster research. These issues include which molecules to measure, which specimens to collect, the timing of specimen collection and processing, and which technologies to use to measure the biomarker and the sensitivity and specificity of the assay system. The article begins with a brief discussion of cytokines and sickness behavior and the role of the cytokines in cancer-related symptoms.