| 1. |
- Gordon, Amy R., et al.
(författare)
-
The scent of disease
- 2015
-
Ingår i: Chemical Senses. - : Oxford University Press (OUP). - 0379-864X .- 1464-3553. ; 40:3, s. 254-254
-
Tidskriftsartikel (refereegranskat)abstract
- Ability to detect diseases in conspecifics would be advantageous for the individual. In line with this, rodents avoid body odors of infected individuals. Two studies (Olsson et al. 20014; in prep.) indicated that this is possible by way of human smell and human observers. T-shirts from donors (worn for 4 hours) that had received an injection of endotoxin [0.8ng lipopolysaccharide (LPS) / kg body weight], which causes systemic inflammation, smelled more unpleasant, intense, and sick than shirts from donors that had received a placebo (Saline) injection. GC/MS analysis of the shirts suggested that the change of body odor was not due to a general increase of odorous compounds in the “sick shirts” compared to “placebo shirts” but rather to a qualitative change. Study 2 (ongoing) further investigated the nature of this perception. In a first experiment, we compared the body odor of 30 endotoxin (0.6ng LPS / kg body weight) and 21 placebo (Saline) donors. Again, body odors were sampled during 4 hours using T-shirts. Observers then smelled the shirts and rated intensity, pleasantness, and disgust. In a second experiment, urine from these donors were collected and was investigated in the same way with subjective ratings. Altogether the data suggest that systemic inflammation makes body odors more aversive within a few hours.
|
|
| 2. |
- Göranson, Sofie Paues, et al.
(författare)
-
Circulating H3Cit is elevated in a human model of endotoxemia and can be detected bound to microvesicles
- 2018
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Early diagnosis of sepsis is crucial since prompt interventions decrease mortality. Citrullinated histone H3 (H3Cit), released from neutrophil extracellular traps (NETs) upon binding of platelets to neutrophils following endotoxin stimulation, has recently been proposed a promising blood biomarker in sepsis. Moreover, microvesicles (MVs), which are released during cell activation and apoptosis and carry a variety of proteins from their parental cells, have also been shown to be elevated in sepsis. In a randomized and placebo-controlled human model of endotoxemia (lipopolysaccharide injection; LPS), we now report significant LPS-induced elevations of circulating H3Cit in 22 healthy individuals. We detected elevations of circulating H3Cit by enzyme-linked immunosorbent assay (ELISA), as well as bound to MVs quantified by flow cytometry. H3Cit-bearing MVs expressed neutrophil and/or platelet surface markers, indicating platelet-neutrophil interactions. In addition, in vitro experiments revealed that H3Cit can bind to phosphatidylserine exposed on platelet derived MVs. Taken together; our results demonstrate that NETs can be detected in peripheral blood during endotoxemia by two distinct H3Cit-specific methods. Furthermore, we propose a previously unrecognized mechanism by which H3Cit may be disseminated throughout the vasculature by the binding to MVs.
|
|
| 3. |
- Lasselin, Julie, et al.
(författare)
-
Lipopolysaccharide Alters Motivated Behavior in a Monetary Reward Task : a Randomized Trial
- 2017
-
Ingår i: Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 0893-133X .- 1740-634X. ; 42:4, s. 801-810
-
Tidskriftsartikel (refereegranskat)abstract
- Inflammation-induced sickness is associated with a large set of behavioral alterations; however, its motivational aspects remain poorly explored in humans. The present study assessed the effect of lipopolysaccharide (LPS) administration at a dose of 2 ng/kg of body weight on motivation in 21 healthy human subjects in a double-blinded, placebo (saline)-controlled, cross-over design. Incentive motivation and reward sensitivity were measured using the Effort Expenditure for Rewards Task (EEfRT), in which motivation for high-effort/high-reward trials vs low-effort/low-reward trials are manipulated by variations in reward magnitude and,probability to win. Because of the strong interactions between sleepiness and motivation, the role of sleepiness was also determined. As expected, the probability to win predicted the choice to engage in high-effort/high-reward trials; however, this occurred at a greater extent after LPS than after saline administration. This effect was related to the level of sleepiness. Sleepiness increased motivation to choose the high-effort/high-reward mode of response, but only when the probability to win was the highest. LPS had no effect on reward sensitivity either directly or via sleepiness. These results indicate that systemic inflammation induced by LPS administration causes motivational changes in young healthy subjects, which are associated with sleepiness. Thus, despite its association with energy-saving behaviors, sickness allows increased incentive motivation when the effort is deemed worthwhile.
|
|
| 4. |
- Lekander, Mats, et al.
(författare)
-
Intrinsic functional connectivity of insular cortex and symptoms of sickness during acute experimental inflammation
- 2016
-
Ingår i: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 56, s. 34-41
-
Tidskriftsartikel (refereegranskat)abstract
- Task-based fMRI has been used to study the effects of experimental inflammation on the human brain, but it remains unknown whether intrinsic connectivity in the brain at rest changes during a sickness response. Here, we investigated the effect of experimental inflammation on connectivity between areas relevant for monitoring of bodily states, motivation, and subjective symptoms of sickness. In a double blind randomized controlled trial, 52 healthy volunteers were injected with 0.6 ng/kg LPS (lipopolysaccharide) or placebo, and participated in a resting state fMRI experiment after approximately 2h 45 minutes. Resting state fMRI data were available from 48 participants, of which 28 received LPS and 20 received placebo. Bilateral anterior and bilateral posterior insula sections were used as seed regions and connectivity with bilateral orbitofrontal and cingulate (anterior and middle) cortices was investigated. Back pain, headache and global sickness increased significantly after as compared to before LPS, while a non-significant trend was shown for increased nausea. Compared to placebo, LPS was followed by increased connectivity between left anterior insula and left midcingulate cortex. This connectivity was significantly correlated to increase in back pain after LPS and tended to be related to increased global sickness, but was not related to increased headache or nausea. LPS did not affect the connectivity from other insular seeds. In conclusion, the finding of increased functional connectivity between left anterior insula and middle cingulate cortex suggests a potential neurophysiological mechanism that can be further tested to understand the subjective feeling of malaise and discomfort during a sickness response.
|
|
| 5. |
- Olsson, Mats J., et al.
(författare)
-
The Scent of Disease : Human Body Odor Contains an Early Chemosensory Cue of Sickness
- 2014
-
Ingår i: Psychological Science. - : SAGE Publications. - 0956-7976 .- 1467-9280. ; 25:3, s. 817-823
-
Tidskriftsartikel (refereegranskat)abstract
- Observational studies have suggested that with time, some diseases result in a characteristic odor emanating from different sources on the body of a sick individual. Evolutionarily, however, it would be more advantageous if the innate immune response were detectable by healthy individuals as a first line of defense against infection by various pathogens, to optimize avoidance of contagion. We activated the innate immune system in healthy individuals by injecting them with endotoxin (lipopolysaccharide). Within just a few hours, endotoxin-exposed individuals had a more aversive body odor relative to when they were exposed to a placebo. Moreover, this effect was statistically mediated by the individuals' level of immune activation. This chemosensory detection of the early innate immune response in humans represents the first experimental evidence that disease smells and supports the notion of a "behavioral immune response" that protects healthy individuals from sick ones by altering patterns of interpersonal contact.
|
|
| 6. |
- Soop, Anne
(författare)
-
Experimental studies on endotoxin infusion in human : evaluation of pharmacological immunomodulation by adenosine and nicotinamide
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Septicaemia and the systemic inflammatory response syndrome (SIRS), is a major cause of mortality among patients in the intensive care units. Inflammation and thrombosis involve multicellular phenomena with activation of leukocytes, platelets and endothelial cells resulting in synthesis and release of various mediators e.g. cytokines, nitric oxide (NO), endothelin and neuropeptide Y, complement factors and reactive oxygen species such as superoxide anions (02-) and its metabolites. Endotoxin (lipopolysaccharide) is a major stimulus for triggering the host response with the subsequent production of pro- and anti-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and IL- 10. Aim: The overall aim of this thesis was to study some response patterns of sepsis and potential modulations in an experimental model where human volunteers receive endotoxin. The work could thereby contribute to increased understanding of sepsis-related mechanisms and pharmacological interventions and hopefully attenuate the inflammatory response. Methods: The studies were performed using endotoxin (2-4 ng/kg BW) intravenously in healthy male volunteers and took place in the intensive care unit at Huddinge University Hospital. All together, 38 volunteers participated in 73 experiments, 32 received endotoxin at one or two occasions. We measured exhaled NO, plasma cGMP, endothelin, neuropeptide Y, haemostatic parameters, complement activation and nitrite/nitrate after endotoxin (E. Coli, Lot G 1) administration of 4 and 2 ng/kg BW respectively. Using double-blind, cross-over design, we investigated the influence of the anti-inflammatory compounds adenosine (in a low continous, intravenous dose, 40 µg/kg/min) as well as nicotinamide (the amide derivate of vitamin B3, in a high oral dose, 4+4 g, 14 and 2 hours preceding the experiment), on inflammatory parameters after endotoxin. Results: Endotoxin provoked clinical signs of inflammation (fever, headache, increased heart rate and decreased diastolic blood pressure) over a period of 4-6 hours. There were no adverse responses. An early increase in orally exhaled NO concentration was observed and cGMP levels were increased. Cardiac output increased by 100%, systemic vascular resistance decreased by 50%. There was activation of the complement system as well as increased arterial endothelin-1 -like immunoreactivity (ET-1-LI) over time. NPY-like immunoreactivity (NPY-LI) remained unchanged. Endotoxin evoked in vivo activation of platelets, leukocytes and endothelial cells, as well as enhancing platelet-leukocyte aggregate formation and thrombin generation. A modest anti-inflammatory effect by adenosine treatment was observed in this study. Adenosine significantly attenuated the endotoxininduced IL-6 response whereas there was no clear effect on the TNF-α response. After oral nicotinamide treatment, there was no effect on the inflammatory parameters (TNF-α, IL-6, IL-8, IL-10 levels or exhaled NO) at the maximum dose that can be administered without inducing side-effects. Conclusion: In conclusion, the present human endotoxaemic model exhibited reproducible results, thereby providing a stable and safe model for randomised studies. Adenosine, in a low continuous intravenous dose, showed only modest immunomodulatory properties. Nicotinamide did not have any anti-inflammatory effects when a high oral dose was given to healthy volunteers receiving endotoxin.
|
|
