Related Experiment Video
Updated: May 31, 2026
07:48
Intravenous Endotoxin Challenge in Healthy Humans: An Experimental Platform to Investigate and Modulate Systemic Inflammation
Published on: May 16, 2016
Contrasting ocular effects of local versus systemic endotoxin
James T Rosenbaum1, April Woods, Jelena Kezic
1Casey Eye Institute, Portland, Oregon 97239, USA. rosenbaj@ohsu.edu
Investigative Ophthalmology & Visual Science
|July 16, 2011
Summary
Systemic endotoxin (lipopolysaccharide [LPS]) exposure desensitizes leukocytes, preventing eye inflammation despite local LPS presence. This explains why injected LPS into the eye causes inflammation, but systemic LPS does not.
Area of Science:
- Ophthalmology
- Immunology
- Microbiology
Background:
- Endotoxin (lipopolysaccharide [LPS]) injection into the mouse eye causes significant cellular infiltrate.
- Systemic LPS administration does not produce a comparable ocular inflammatory effect, creating a scientific discrepancy.
Purpose of the Study:
- To investigate the reasons behind the discordant inflammatory responses to local versus systemic LPS administration in the murine eye.
- To test hypotheses explaining the lack of ocular inflammation following systemic LPS exposure.
Main Methods:
- BALB/c mice received intravitreal (ivt) or intraperitoneal (ip) injections of Escherichia coli LPS.
- Uveitis was assessed using microscopy; cytokine levels were measured via ELISA.
- Leukocyte diapedesis was evaluated by simultaneous ivt and ip LPS administration.
Main Results:
- Local LPS (250 ng ivt) induced significant leukocytic infiltrate, while high-dose systemic LPS (100 microg ip) did not.
- Systemic LPS induced comparable ocular cytokine levels to local LPS, disproving reduced cytokine induction as the cause.
- Systemic LPS co-administration blocked the typical cellular infiltrate seen with ivt LPS, without affecting leukocyte rolling or sticking.
Conclusions:
- Systemic and local LPS exposure elicit distinct effects on ocular inflammation in mice.
- Systemic LPS likely desensitizes leukocytes, inhibiting their transmigration and explaining the lack of ocular inflammation despite local endotoxin presence.
Related Concept Videos
01:12Local Anesthetics: Adverse Effects
While local anesthetics are generally safe and well-tolerated, they can occasionally cause adverse effects that vary in severity. Local anesthetics can induce toxicity at two distinct levels. They can either produce local effects through direct contact with the neural elements or be absorbed into the bloodstream from the injection site, leading to systemic effects.
Once absorbed into the systemic circulation, local anesthetics can affect the organs that depend on the functioning of sodium...
Once absorbed into the systemic circulation, local anesthetics can affect the organs that depend on the functioning of sodium...
01:25Acute Inflammation III: Local and Systemic Effects
Acute inflammation produces a coordinated set of local and systemic changes that limit injury, eliminate pathogens, and initiate repair. These responses arise within minutes of infection, trauma, or chemical insult and are driven by vascular alterations and leukocyte-derived mediators. When the stimulus resolves, the reaction typically abates within days.Local EffectsAt the site of injury, arteriolar vasodilation increases blood flow, resulting in redness and warmth. Simultaneously, increased...
01:26Toxic Reactions: Overview
When toxic substances penetrate the human body, they disseminate to various tissues, undergoing metabolic changes. This process yields reactive metabolites that may covalently bind with specific target molecules, resulting in toxicity.
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
01:22Microbiome of the Eye
The human eye has a specialized microbiota that reflects its unique anatomical and immunological environment. This low-biomass microbial community predominantly colonizes the conjunctiva and eyelid margins, playing a vital role in ocular surface homeostasis and defense. Despite its proximity to the richly colonized facial skin, the ocular surface maintains a distinct microbial profile due to continuous mechanical and biochemical defense mechanisms.The conjunctival surface hosts fewer microbial...