Biomedical Informatics Research Case Study: The Role of IL-6 in Rheumatoid Arthritis

This article is missing the resource searching screen shots as originally published.

Rheumatoid arthritis is a debilitating autoimmune disease. I heard somewhere, sometime ago, the protein IL-6 is involved with rheumatoid arthritis. I have a previous, even if limited, understanding that the protein CRP is secreted by the liver for inflammatory purposes in response to the disease. But I do not understand what role IL-6 plays; where it is produced, whether it is a component of the rouge immune system itself or in response to the damage created by the immune system. I am not even sure for what IL-6 is an acronym. Let’s find out.

The following is a research log detailing the process of understanding the role IL-6 plays in the disease rheumatoid arthritis and ultimately understanding the basic functions of the IL-6 protein in Homo sapiens.

1. First let’s get a basic understanding of IL-6. For this let’s do some basic vocabulary searches (google/dictionary, NCIt and NCIm).

Google: A google search of IL-6 brought up the full name Interleukin 6, an image of its crystallized structure and a brief about its function as a pro-inflammatory cytokine and an anti-inflammatory myokine, coded in humans by the IL6 gene. It also provided a wikipedia entry for us.

Wikipedia: the wikipedia entry found via google provides us with some key concepts about where the protein comes from and why. “Interleukin 6 is secreted by T cells and macrophages to stimulate immune response, e.g. during infection and after trauma, especially burns or other tissue damage leading to inflammation. IL-6 also plays a role in fighting infection, as IL-6 has been shown in mice to be required for resistance against bacterium Streptococcus pneumoniae.”

NCIt and NCIm: I now have some questions for NCIt/NCIm. I will start with exact name searches of cytokine and myokine to get an understanding of protein class of IL6.

Cytokine from NCIt:

In addition to a definition we also can see related terms:

We also can see synonyms. I checked that tab and it was essentially empty.

Cytokine from NCIm:

Myokine:

Myokine: Nothing was found by either NCIt or NCIm even when the search was modified to contain the word myokine. But Google produced the following definition with a link to widipedia.

2. Next, let’s try the Health Science databases. Browsing the GF Smith Health Sciences Databases, I find two dbs related to genetics, Gene and Genome. I click through into the Gene database to run an IL6 search.

Gene Database

I find there are many entries for IL6 genes for various species. The first one is

Homo Sapiens, so I click through to get the detail page which gives a trove of valuable information about the function of IL6: “[IL6] functions in inflammation and the maturation of B cells”, “[IL6] is primarily produced at the sites of acute and chronic inflammation” and “[IL-6 is] capable of inducing fever in people with autoimmune diseases or infections.” But the best part is, if I scroll down I can get a link to PubMed, prepopulated with all 3644 IL6 citations.

Let’s click on through to PubMed and get into the meat of the research.

3. PubMed is always a good source.

I immediately go into the PubMed advanced search to filter my IL6 citation list for those containing rheumatoid arthritis. I create a separate search for the disease, then I combine both searches (linked from Gene DB) with the AND boolean operator. I end up with a total of 117 publications. I browse through the list looking for something that will indicate the function of IL6 in the disease. I notice one article in particular: Interleukin-6 as a therapeutic target. This is of interest because the topic “therapeutic target” suggests it will have information on the function of IL6 and how to either increase or decrease that function. Upon reading the abstract, and excerpts of the paper, I find that anti-IL6 therapies have been shown to reduce inflammation in rheumatoid arthritis. The paper even has a couple of diagrams outlining the various biological processes in which IL6 is involved. I’ll keep this paper in my back pocket so I can check its quality on Web of Science.

4. Web of Science is an invaluable resource. It allows us to quantify and better understand the quality of our sources by seeing citation metrics. I search for the title of the paper I found in PuBmed.

It proves to be a highly cited paper, with 36 citations since March 2015, even getting one of those gold cup icons. I am happy with my gold standard findings.

5. Next, let’s see what MEDLINE can find for us. First thing I do in MEDLINE is search for IL6. I want to inspect the subject headings to see if any of the related terms are relevant for this topic.

I notice that is lists out all the interleukins from that class. So it seems to be I want to focus my query so it only pulls out papers with IL6 as the main subject. I continue and select the subject headings I feel are relevant to us finding the function of IL6.

I now do the same query for rheumatoid arthritis. Here I want to expand on the search terms to ensure I capture all the subclasses of rheumatoid arthritis.

I now have two searches, each optimized for query terms and subject headings. When I combine them together with an AND Boolean operator I obtain 523 results. It is a large number but very manageable. In fact almost all of the papers I look through have some information on the function of IL6 in rheumatoid arthritis within their abstracts. And they seem to be in-line with that high quality paper I found from PubMed via NIH Gene DB

Summary

In the end I was able to figure out that IL6 is secreted by a number of different cell types for the purposes of inflammation and fever. It is secreted near the site of acute or chronic inflammation and hence is directly associated with rheumatoid arthritis. Efforts to block IL6 have shown reduced inflammation and localized fever in rheumatoid arthritis.